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.

Optical beam scanner with reconfigurable non-mechanical control of beam position, angle, and focus for low-cost whole-eye OCT imaging.

Whole-eye optical coherence tomography (OCT) imaging is a promising tool in ocular biometry for cataract surgery planning, glaucoma diagnostics and myopia progression studies. However, conventional OCT systems are set up to perform either anterior or posterior eye segment scans and cannot easily switch between the two scan configurations without adding or exchanging optical components to account for the refraction of the eye's optics. Even in state-of-the-art whole-eye OCT systems, the scan configurations are pre-selected and cannot be dynamically reconfigured. In this work, we present the design, optimization and experimental validation of a reconfigurable and low-cost optical beam scanner based on three electro-tunable lenses, capable of non-mechanically controlling the beam position, angle and focus. We derive the analytical theory behind its control. We demonstrate its use in performing alternate anterior and posterior segment imaging by seamlessly switching between a telecentric focused beam scan to an angular collimated beam scan. We characterize the corresponding beam profiles and record whole-eye OCT images in a model eye and in an ex vivo rabbit eye, observing features comparable to those obtained with conventional anterior and posterior OCT scanners. The proposed beam scanner reduces the complexity and cost of other whole-eye scanners and is well suited for 2-D ocular biometry. Additionally, with the added versatility of seamless scan reconfiguration, its use can be easily expanded to other ophthalmic applications and beyond.

Estimation of the full shape of the crystalline lens from OCT: validation using stretched donor lenses.

Quantifying human crystalline lens geometry as a function of age and accommodation is important for improved cataract and presbyopia treatments. In previous works we presented eigenlenses as a basis of 3-D functions to represent the full shape of the crystalline lens ex vivo. Also, we presented the application of eigenlenses to estimate the full shape of the lens in vivo from 3-D optical coherence tomography (OCT) images, where only the central part of the lens -visible through the pupil- is available. The current work presents a validation of the use of eigenlenses to estimate in vivo the full shape of dis-accommodated lenses. We used 14 ex vivo crystalline lenses from donor eyes (11-54 y/o) mounted in a lens stretcher, and measured the geometry and the power of the lenses using a combined OCT and ray tracing aberrometry system. Ex vivo, the full extent of the lens is accessible from OCT because the incident light is not blocked by the iris. We measured in non-stretched (fully accommodated) and stretched (mimicking in vivo dis-accommodated lenses) conditions. Then, we simulated computationally in vivo conditions on the obtained ex vivo lenses geometry (assuming that just the portion of the lens within a given pupil is available), and estimated the full shape using eigenlenses. The mean absolute error (MAE) between estimated and measured lens' diameters and volumes were MAE = 0.26 ± 0.18 mm and MAE = 7.0 ± 4.5 mm3, respectively. Furthermore, we concluded that the estimation error between measured and estimated lenses did not depend on the accommodative state (change in power due to stretching), and thus eigenlenses are also useful for the full shape estimation of in vivo dis-accommodated lenses.

Computational simulation of the optical performance of an EDOF intraocular lens in post-LASIK eyes.

PURPOSE: To evaluate computationally the optical performance of AcrySof IQ Vivity extended depth-of-focus (EDOF) intraocular lenses (IOLs) in post-laser in situ keratomileusis (LASIK) eyes. SETTING: Visual Optics and Biophotonics Laboratory, Madrid, Spain. DESIGN: Experimental study. METHODS: Computer pseudophakic eye models were implemented using reported post-LASIK corneal aberrations (refractive corrections from -7.5 to +4.5 diopters [D]) and virtually implanted with monofocal (AcrySof IQ) or EDOF (AcrySof IQ Vivity) IOLs. Retinal image quality was quantified through visual Strehl (VS). The depth of focus (DOF) was calculated from the through-focus VS curves. Halos were estimated from the light spread in the image of a pinhole. Those quantitative parameters were obtained for 5.0 and 3.0 mm pupil diameters. RESULTS: Simulated virgin eyes showed VS of 0.89/0.99 with monofocal IOLs and 0.74/0.52 with EDOF IOLs for 5.0/3.0 mm pupils at best focus. VS decreased with induced spherical aberration (SA) by 25% and with induced SA + coma by 61% on average (3.0 mm pupils). The DOF was 2.50 D in virgin eyes with EDOF IOLs, 1.66 ± 0.30 and 2.54 ± 0.31 D ( P < .05) on average in post-LASIK eyes for 3.0 mm pupils, monofocal and EDOF IOLs, respectively. Halos were more sensitive to SA induction for 5.0 mm pupils, and induction of positive SA (myopic LASIK) resulted in reduced halos with the EDOF when compared with the monofocal IOLs, by 1.62 (SA) and 1.86 arc min (SA + coma), on average. CONCLUSIONS: Computer post-LASIK pseudophakic eye models showed that the DOF was less dependent on the presence of SA and coma with EDOF IOLs and that halos were reduced with EDOF IOLs compared with the monofocal IOL for a range of SA.

Effect of fixational eye movements in corneal topography measurements with optical coherence tomography.

There is an increasing interest in applying optical coherence tomography (OCT) to quantify the topography of ocular structures. However, in its most usual configuration, OCT data is acquired sequentially while a beam is scanned through the region of interest, and the presence of fixational eye movements can affect the accuracy of the technique. Several scan patterns and motion correction algorithms have been proposed to minimize this effect, but there is no consensus on the ideal parameters to obtain a correct topography. We have acquired corneal OCT images with raster and radial patterns, and modeled the data acquisition in the presence of eye movements. The simulations replicate the experimental variability in shape (radius of curvature and Zernike polynomials), corneal power, astigmatism, and calculated wavefront aberrations. The variability of the Zernike modes is highly dependent on the scan pattern, with higher variability in the direction of the slow scan axis. The model can be a useful tool to design motion correction algorithms and to determine the variability with different scan patterns.

Estimation of the full shape of the crystalline lens in-vivo from OCT images using eigenlenses.

Quantifying the full 3-D shape of the human crystalline lens is important for improving intraocular lens power or sizing calculations in treatments of cataract and presbyopia. In a previous work we described a novel method for the representation of the full shape of the ex vivo crystalline lens called eigenlenses, which proved more compact and accurate than compared state-of-the art methods of crystalline lens shape quantification. Here we demonstrate the use of eigenlenses to estimate the full shape of the crystalline lens in vivo from optical coherence tomography images, where only the information visible through the pupil is available. We compare the performance of eigenlenses with previous methods of full crystalline lens shape estimation, and demonstrate an improvement in repeatability, robustness and use of computational resources. We found that eigenlenses can be used to describe efficiently the crystalline lens full shape changes with accommodation and refractive error.

Long-range frequency-domain optical delay line based on a spinning tilted mirror for low-cost ocular biometry.

Optical biometers are routinely used to measure intraocular distances in ophthalmic applications such as cataract surgery planning or myopia monitoring. However, due to their high cost and reduced transportability, access to them for screening and surgical planning is still limited in low-resource and remote settings. To increase patients' access to optical biometry we propose a novel low-cost frequency-domain optical delay line (FD-ODL) based on an inexpensive stepper motor spinning a tilted mirror, for integration into a time-domain (TD)-biometer, amenable to a compact footprint. In the proposed FD-ODL, the axial scan range and the A-scan rate are decoupled from one another, as the former only depends on the spinning mirror tilt angle, while the A-scan rate only depends on the motor shaft rotational speed. We characterized the scanning performance and specifications for two spinning mirror tilt angles, and compared them to those of the standard, more expensive FD-ODL implementation, employing a galvanometric scanner for group delay generation. A prototype of the low-cost FD-ODL with a 1.5 deg tilt angle, resulting in an axial scan range of 6.61 mm and an A-scan rate of 10 Hz was experimentally implemented and integrated in a dual sample beam optical low-coherence reflectometry (OLCR) setup with a detour unit to replicate the measurement window around the anterior segment and the retina. The intraocular distances of a model eye were measured with the proposed low-cost biometer and found to be in good agreement with those acquired by a custom swept-source optical coherence tomography (SS-OCT) system and two commercial biometers, validating our novel design.

Matching convolved images to optically blurred images on the retina.

Convolved images are often used to simulate the effect of ocular aberrations on image quality, where the retinal image is simulated by convolving the stimulus with the point spread function derived from the subject's aberrations. However, some studies have shown that convolved images are perceived far more degraded than the same image blurred with optical defocus. We hypothesized that the positive interactions between the monochromatic and chromatic aberrations in the eye are lost in the convolution process. To test this hypothesis, we evaluated optical and visual quality with natural optics and with convolved images (on-bench, computer simulations, and visual acuity [VA] in subjects) using a polychromatic adaptive optics system with monochromatic (555 nm) and polychromatic light (WL) illumination. The subject's aberrations were measured using a Hartmann Shack system and were used to convolve the visual stimuli, using Fourier optics. The convolved images were seen through corrected optics. VA with convolved stimuli was lower than VA through natural aberrations, particularly in WL (by 26% in WL). Our results suggest that the systematic decrease in visual performance with visual acuity and retinal image quality by simulation with convolved stimuli appears to be primarily associated with a lack of favorable interaction between chromatic and monochromatic aberrations in the eye.

Evaluating the effect of ocular aberrations on the simulated performance of a new refractive IOL design using adaptive optics.

Adaptive optics (AO) visual simulators are excellent platforms for non-invasive simulation visual performance with new intraocular lens (IOL) designs, in combination with a subject own ocular aberrations and brain. We measured the through focus visual acuity in subjects through a new refractive IOL physically inserted in a cuvette and projected onto the eye's pupil, while aberrations were manipulated (corrected, or positive/negative spherical aberration added) using a deformable mirror (DM) in a custom-developed AO simulator. The IOL increased depth-of-focus (DOF) to 1.53 ± 0.21D, while maintaining high Visual Acuity (VA, -0.07 ± 0.05), averaged across subjects and conditions. Modifying the aberrations did not alter IOL performance on average.

Accommodation through simulated multifocal optics.

We evaluated the interaction of multifocal patterns with eye's accommodation. Seven patterns were mapped on the spatial light modulator and the deformable mirror of an adaptive optics visual simulator, and projected onto the subjects' eyes, representing different contact lens designs: NoLens, Bifocal Center Distance (+2.50D), Bifocal Center Near (+2.50D) and Multifocal Center Near-MediumAdd (+1.75D) and Center Near HighAdd (+2.50D), positive and negative spherical aberration (±1µm). The change in spherical aberration and the accommodative response to accommodative demands were obtained from Hartmann-Shack measurements. Positive spherical aberration and Center Distance designs are consistent with a higher accommodative response (p=0.001 & p=0.003): steeper shift of SA towards negative values and lower accommodative lag.

Optical and visual quality of real intraocular lenses physically projected on the patient's eye.

Visual simulators aim at evaluating vision with ophthalmic corrections prior to prescription or implantation of intraocular lenses (IOLs) in the patient's eye. In the present study, we present the design, implementation, and validation of a new IOL-in-cuvette channel in an Adaptive Optics visual simulator, which provides an alternative channel for pre-operative simulation of vision with IOLs. The IOL is projected on the pupil's plane of the subject by using a Rassow system. A second lens, the Rassow lens, compensates for an IOL of 20 D while other powers can be corrected with a Badal system within a 5 D range. The new channel was evaluated by through-focus (TF) optical quality in an artificial eye on bench, and by TF visual acuity in patients, with various IOL designs (monofocal, diffractive trifocal, and refractive extended depth of focus).

Simulating Outcomes of Cataract Surgery: Important Advances in Ophthalmology.

As the human eye ages, the crystalline lens stiffens (presbyopia) and opacifies (cataract), requiring its replacement with an artificial lens [intraocular lens (IOL)]. Cataract surgery is the most frequently performed surgical procedure in the world. The increase in IOL designs has not been paralleled in practice by a sophistication in IOL selection methods, which rely on limited anatomical measurements of the eye and the surgeon's interpretation of the patient's needs and expectations. We propose that the future of IOL selection will be guided by 3D quantitative imaging of the crystalline lens to map lens opacities, anticipate IOL position, and develop fully customized eye models for ray-tracing-based IOL selection. Conversely, visual simulators (in which IOL designs are programmed in active elements) allow patients to experience prospective vision before surgery and to make more informed decisions about which IOL to choose. Quantitative imaging and optical and visual simulations of postsurgery outcomes will allow optimal treatments to be selected for a patient undergoing modern cataract surgery.

Isolated human crystalline lens three-dimensional shape: A comparison between Indian and European populations.

There have been many studies on lens properties in specific populations (e.g. in China, Europe, Singapore, etc.) some of which suggest there may be differences between populations. Differences could be caused by ethnic or environmental influences or experimental procedures. The purpose of this study is to evaluate if any differences exist between Indian and European populations in the central geometric and full shape properties of human lenses. Two custom-developed spectral domain optical coherence tomography systems were used to acquire the crystalline lens geometry: one in India (69 lenses from 59 donors) and the other in Spain (24 lenses from 19 donors). The steps for obtaining accurate 3-D models from optical coherence tomography raw images comprised of image segmentation, fan and optical distortion correction, tilt removal and registration. The outcome variables were lens equatorial diameter, lens thickness, anterior and posterior lens thicknesses and their ratio, central radius of curvature of the anterior and posterior lens surfaces, lens volume and lens surface area. A mixed effects model by maximum likelihood estimation was used to evaluate the effect of age, population and their interaction (age*population) on lens parameters. After adjusting for age, there were no population differences observed in anterior and posterior radii of curvature, equatorial diameter, lens thickness, anterior and posterior lens thicknesses and their ratio, volume and surface area (all p ≥ 0.08). There was also no effect of the interaction term on anterior and posterior radii of curvature, equatorial diameter, lens thickness, anterior and posterior lens thicknesses and their ratio, volume and surface area (all p ≥ 0.06). All central geometric and full shape parameters appeared to be comparable between the European and Indian populations. This is the first study to compare geometric and full shape lens parameters between different populations in vitro.

Eigenlenses: a new model for full crystalline lens shape representation and its applications.

The crystalline lens is an important optical element in the eye, responsible for focusing, and which experiences significant changes throughout life. The shape of the lens is usually studied only in the optical area (central 4 to 6 mm). However, for a great number of applications, a description of the full shape of the crystalline lens is required. We propose a new method for the representation of the full shape of the crystalline lens, constructed from 3-dimensional optical coherence tomography images of 133 isolated crystalline lenses (0-71 y/o), which we have called eigenlenses. The method is shown to be compact and accurate to describe not only the full shape of the crystalline lens, but also the optical zone in comparison with other methods. We also demonstrate its application to the extrapolation of the full shape of the crystalline lens from in-vivo optical images of the anterior segment of the eye, where only the central part of the lens visible through the pupil is available, and in the generation (synthesis) of realistic full lenses of a given age. The method has critical applications, among others, in improving and evaluating myopia and presbyopia treatments.

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.

Arthropod biodiversity patterns point to the Mesovoid Shallow Substratum (MSS) as a climate refugium.

The determinants of biodiversity patterns in the subterranean habitat called Mesovoid Shallow Substratum (MSS) are not well-understood. In this study, thirty-three scree slopes at high altitudes were selected across the Sierra de Guadarrama National Park in central Spain to investigate the effect of ten environmental variables on the abundance and species diversity of the spider and springtail assemblages from the colluvial MSS. In each locality, a multiperforated PVC tube with a pitfall trap inside was buried up to 1 m deep, and generalized linear models and Mantel tests were used to analyze the effect of mainly climate- and habitat-related variables on the diversity patterns of both taxa. A total of 1143 individual spiders belonging to 54 species and 40 811 springtail individuals belonging to 62 species were collected. The analyses indicated that cold temperatures and the presence of forest cover on the surface significantly enhance richness and abundance in the two taxa. Environmental similarity also had a small positive effect on faunistic similarity. However, the effects of temperature and habitat detected on spider richness and abundance were stronger than on springtails, whereas the reverse was found regarding faunistic similarity. These results indicate that subterranean dwellers respond differently to the same environmental factors, which in turn, points to a different degree of affinity for the MSS. The MSS plays an important role in the survival of high mountain arthropod species, acting as a climate refuge, so the protection of this habitat should be prioritized.

Age-Related Changes to the Three-Dimensional Full Shape of the Isolated Human Crystalline Lens.

Purpose: Studying the full shape crystalline lens geometry is important to understand the changes undergone by the crystalline lens leading to presbyopia, cataract, or failure of emmetropization, and to aid in the design and selection of intraocular lenses and new strategies for correction. We used custom-developed three-dimensional (3-D) quantitative optical coherence tomography (OCT) to study age-related changes in the full shape of the isolated human crystalline lens. Methods: A total of 103 ex vivo human isolated lenses from 87 subjects (age range, 0-56 years) were imaged using a 3-D spectral-domain OCT system. Lens models, constructed after segmentation of the surfaces and distortion correction, were used to automatically quantify central geometric parameters (lens thickness, radii of curvatures, and asphericities of anterior and posterior surfaces) and full shape parameters (lens volume, surface area, diameter, and equatorial plane position). Age-dependencies of these parameters were studied. Results: Most of the measured parameters showed a biphasic behavior, statistically significantly increasing (radii of curvature, lens volume, surface area, diameter) or decreasing (asphericities, lens thickness) very fast in the first two decades of life, followed by a slow but significant increase after age 20 years (for all the parameters except for the posterior surface asphericity and the equatorial plane position, that remained constant). Conclusions: Three-dimensional quantitative OCT allowed us to study the age-dependency of geometric parameters of the full isolated human crystalline lens. We found that most of the lens geometric parameters showed a biphasic behavior, changing rapidly before age 20 years and with a slower linear growth thereafter.

Crystalline lens gradient refractive index distribution in the guinea pig.

PURPOSE: The crystalline lens undergoes morphological and functional changes with age and may also play a role in eye emmetropisation. Both the geometry and the gradient index of refraction (GRIN) distribution contribute to the lens optical properties. We studied the lens GRIN in the guinea pig, a common animal model to study myopia. METHODS: Lenses were extracted from guinea pigs (Cavia porcellus) at 18 days of age (n = 4, three monolaterally treated with negative lenses and one untreated) and 39 days of age (n = 4, all untreated). Treated eyes were myopic (-2.07 D on average) and untreated eyes hyperopic (+3.3 D), as revealed using streak retinoscopy in the live and cyclopeged animals. A custom 3D spectral domain optical coherence tomography (OCT) system (λ = 840 nm, Δλ = 50 nm) was used to image the enucleated crystalline lens at two orientations. Custom algorithms were used to estimate the lens shape and GRIN was modelled with four variables that were reconstructed using the OCT data and a minimisation algorithm. Ray tracing was used to calculate the optical power and spherical aberration assuming a homogeneous refractive index or the estimated GRIN. RESULTS: Guinea pig lenses exhibited nearly parabolic GRIN profiles. When comparing the two age groups (18- and 39 day-old) there was a significant increase in the central thickness (from 3.61 to 3.74 mm), and in the refractive index of the surface (from 1.362 to 1.366) and the nucleus (from 1.443 to 1.454). The presence of GRIN shifted the spherical aberration (-4.1 µm on average) of the lens towards negative values. CONCLUSIONS: The guinea pig lens exhibits a GRIN profile with surface and nucleus refractive indices that increase slightly during the first days of life. GRIN plays a major role in the lens optical properties and should be incorporated into computational guinea pig eye models to study emmetropisation, myopia development and ageing.

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.

Off-axis optical coherence tomography imaging of the crystalline lens to reconstruct the gradient refractive index using optical methods.

Earlier studies have shown that the gradient index of refraction (GRIN) of the crystalline lens can be reconstructed in vitro using Optical Coherence Tomography (OCT) images. However, the methodology cannot be extended in vivo because it requires accurate measurements of the external geometry of the lens. Specifically, the posterior surface is measured by flipping the lens so that the posterior lens surface faces the OCT beam, a method that cannot be implemented in vivo. When the posterior surface is imaged through the lens in its natural position, it appears distorted by the unknown GRIN. In this study, we demonstrate a method to reconstruct both the GRIN and the posterior surface shape without the need to flip the lens by applying optimization routines using both on-axis and off-axis OCT images of cynomolgous monkey crystalline lenses, obtained by rotating the OCT delivery probe from -45 to +45 degrees in 5 degree steps. We found that the GRIN profile parameters can be reconstructed with precisions up to 0.009, 0.004, 1.7 and 1.1 (nucleus and surface refractive indices, and axial and meridional power law, respectively), the radius of curvature within 0.089 mm and the conic constant within 0.3. While the method was applied on isolated crystalline lenses, it paves the way to in vivo lens GRIN and posterior lens surface reconstruction.