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.

Poster Session: Experimental assessment of scleral anisotropy using multi-meridian air-coupled ultrasonic optical coherence elastography.

Scleral biomechanics plays a key role in the understanding of myopia progression. In this study, we characterized the elastic properties of sclera using an air-coupled ultrasonic (ACUS) optical coherence elastography (OCE) system. New Zealand rabbit eyes (n=7) were measured (<24hr postmortem) in four scleral locations: superior/inferior temporal (ST, IT), and superior/inferior nasal (SN, IN) maintaining an intraocular pressure of 15 mmHg. Elastic waves were induced in the sclera, and wave propagation velocity and shear modulus were measured along two directions: circumferential (superior-inferior) and meridional (nasal-temporal). Wave velocity in scleral tissue ranged from 6 to 24 m/s and shear modulus from 11 to 150 kPa. Velocity was significantly higher (p<.001) in the circumferential vs. meridional directions in the following locations: ST:15.83±2.85 vs 9.43±1.68 m/s, IT:15.00±3.98 vs 8.93±1.53 m/s; SN:16.79±4.30 vs 9.27±1.47 m/s; and IN:13.92±3.85 vs 8.57±1.46 m/s. The average shear modulus in the circumferential was also significantly higher (p<.001) than in the meridional direction for all locations: 65.37±6.04 vs 22.55±1.36 kPa. These results show that the rabbit sclera is mechanically anisotropic with higher rigidity in the circumferential direction compared to the meridional direction. ACUS-OCE is a promising non-invasive method to quantify the biomechanical changes in scleral tissue for future studies involving myopia treatments.

Poster Session: Estimation of scleral biomechanical properties from air-puff-coupled optical coherence tomography.

Progression of myopia is usually accompanied by axial overgrowth of the eyeball, which affects scleral biomechanics (BM). To study scleral biomechanics, we propose the use of air-puff deformation swept-source OCT imaging. Air-puff deformation imaging was performed at different sites of ex vivo porcine (n=5) and rabbit (n=3) eyes, (<24hr postmortem): Nasal/temporal equatorial and posterior sclera (NE, NP, TE, TP), superior (S) and inferior (I) sclera, and cornea (C). Intraocular pressure was kept at 15mmHg. Deformation data were used as input to inverse finite element model (FEM) algorithms to reconstruct BM properties. Experimental deformation amplitudes showed dependence on the animal model, with porcine scleras exhibiting greater inter-site variation (displacement of S, I was up to four times greater than that of N, T), while rabbit scleras exhibited at most 40% of displacement differences between all sites. Both models showed significant (p<.001) differences in the temporal deformation profile between sclera and (C), but similarities in all scleral locations, suggesting that the scleral temporal profile is independent of scleral thickness variations. The FEM estimated an elastic modulus of 1.84 ± 0.30 MPa (I) to 6.04 ± 2.11 MPa (TE) for the porcine sclera. The use of scleral air-puff imaging is promising for noninvasive investigation of structural changes in the sclera associated with myopia and for monitoring possible modulation of scleral stiffness with myopia treatment.

Estimation of Crystalline Lens Material Properties From Patient Accommodation Data and Finite Element Models.

Purpose: The mechanical properties of the crystalline lens are related to its optical function of accommodation, and their changes with age are one of the potential causes for presbyopia. We estimated the mechanical parameters of the crystalline lens using quantitative optical coherence tomography (OCT) imaging and wavefront sensing data from accommodating participants and computer modeling. Methods: Full-lens shape data (from quantitative swept-source OCT and eigenlens representation) and optical power data (from Hartmann-Shack wavefront sensor) were obtained from 11 participants (22-30 years old) for relaxed accommodation at infinity and -4.5 D accommodative demand. Finite element models of lens, capsular bag, zonulae, and ciliary body were constructed using measured lens geometry and literature data, assuming a 60-mN radial force. An inverse modeling scheme was used to determine the shear moduli of the nucleus and cortex of the lens, such that the simulated deformed (maximally stretched) lens matched the participant's lens at -4.5 D. Results: The shear moduli of the nucleus and cortex were 1.62 ± 1.32 and 8.18 ± 5.63 kPa, on average, respectively. The shear modulus of the nucleus was lower than that of the cortex for all participants evaluated. The average of the two moduli per participant was statistically significantly correlated with age (R2 = 0.76, P = 0.0049). Conclusions: In vivo imaging and mechanical modeling of the crystalline lens allow estimations of the crystalline lens' mechanical properties. Differences between nuclear and cortical moduli and their dependency with age appear to be critical in accommodative function and likely in its impairment in presbyopia.

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.

Combination of protein and cell internalization SELEX identifies a potential RNA therapeutic and delivery platform to treat EphA2-expressing tumors.

The EphA2 receptor tyrosine kinase is overexpressed in most solid tumors and acts as the major driver of tumorigenesis. In this study, we developed a novel approach for targeting the EphA2 receptor using a 2'-fluoro-modified pyrimidine RNA aptamer termed ATOP. We identified the ATOP EphA2 aptamer using a novel bioinformatics strategy that compared aptamers enriched during a protein SELEX using recombinant human EphA2 and a cell-internalization SELEX using EphA2-expressing MDA231 tumor cells. When applied to EphA2-expressing tumor cell lines, the ATOP EphA2 aptamer attenuated tumor cell migration and clonogenicity. In a mouse model of spontaneous metastasis, the ATOP EphA2 aptamer slowed primary tumor growth and significantly reduced the number of lung metastases. The EphA2 ATOP aptamer represents a promising candidate for the development of next-generation targeted therapies that provide safer and more effective treatment of EphA2-overexpressing tumors.

Introduction to the Feature Issue on Adaptive Optics for Biomedical Applications.

The guest editors introduce a feature issue commemorating the 25th anniversary of adaptive optics in biomedical research.

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.

In situ enzymatic generation of Au/Pt nanoparticles as an analytical photometric system: proof of concept determination of tyramine.

In situ enzymatic generation of bimetallic nanoparticles, mainly Au/Pt, overcomes the drawbacks (continuous absorbance drift, modest LOQ, and long-time reaction) observed when AuNP alone are produced. In this study, Au/Pt nanoparticles have been characterized by EDS, XPS, and HRTEM images using the enzymatic determination of tyramine with tyramine oxidase (TAO) as a model. Under experimental conditions, the Au/Pt NPs show an absorption maximum at 580 nm which can be related to the concentration of tyramine in the range 1.0 × 10-6M to 2.5 × 10-4M with a RSD of 3.4% (n = 5, using 5 × 10-6M tyramine). The Au/Pt system enables low LOQ (1.0 × 10-6 M), high reduction of the absorbance drift, and a significant shortening of the reaction time (i.e., from 30 to 2 min for a [tyramine] = 1 × 10-4M); additionally, a better selectivity is also obtained. The method has been applied to tyramine determination in cured cheese and no significant differences were obtained compared to a reference method (HRP:TMB). The effect of Pt(II) seems to involve the previous reduction of Au(III) to Au(I) and NP generation from this oxidation state. Finally, a three-step (nucleation-growth-aggregation) kinetic model for the generation of NPs is proposed; this has enabled us to obtain a mathematical equation which explains the experimentally observed variation of the absorbance with time.

Monovision Correction Preference and Eye Dominance Measurements.

Purpose: To propose new methods for eye selection in presbyopic monovision corrections. Methods: Twenty subjects with presbyopia performed two standard methods of binary eye dominance identification (sensory with +1.50 diopters [D ]and +0.50 D and sighting with "hole-in-the-card") and two psychophysical methods of perceived visual quality: (1) the Preferential test, 26 natural images were judged with the near addition in one eye or in the other in a 2-interval forced-choice task, and the Eye Dominance Strength (EDS) defined as the proportion of trials where one monovision is preferred over the other; (2) the Multifocal Acceptance Score (MAS-2EV) test, the perceived quality of a natural images set (for 2 luminance levels and distances) was scored and EDS defined as the score difference between monovision in one eye or the other. Left-eye and right-eye dominance are indicated with negative and positive values, respectively. Tests were performed using a Simultaneous Vision Simulator, which allows rapid changes between corrections. Results: Standard sensory and sighting dominances matched in only 55% of subjects. The Preferential EDS (ranging from -0.7 to +0.9) and MAS-2EV EDS (ranging from -0.6 to +0.4) were highly correlated. Selecting the eye for far in monovision with the MAS-2EV, sensory, or sighting tests would have resulted in 79%, 64%, and 43% success considering the Preferential test as the gold standard. Conclusions: Tests based on perceptual preference allow selection of the preferred monovision correction and measurement of dominance strength. Translational Relevance: The binocular visual simulator allows efficient implementation of eye preference tests for monovision in clinical use.

Tectomer-Mediated Optical Nanosensors for Tyramine Determination.

The development of optical sensors for in situ testing has become of great interest in the rapid diagnostics industry. We report here the development of simple, low-cost optical nanosensors for the semi-quantitative detection or naked-eye detection of tyramine (a biogenic amine whose production is commonly associated with food spoilage) when coupled to Au(III)/tectomer films deposited on polylactic acid (PLA) supports. Tectomers are two-dimensional oligoglycine self-assemblies, whose terminal amino groups enable both the immobilization of Au(III) and its adhesion to PLA. Upon exposure to tyramine, a non-enzymatic redox reaction takes place in which Au(III) in the tectomer matrix is reduced by tyramine to gold nanoparticles, whose reddish-purple color depends on the tyramine concentration and can be identified by measuring the RGB coordinates (Red-Green-Blue coordinates) using a smartphone color recognition app. Moreover, a more accurate quantification of tyramine in the range from 0.048 to 10 µM could be performed by measuring the reflectance of the sensing layers and the absorbance of the characteristic 550 nm plasmon band of the gold nanoparticles. The relative standard deviation (RSD) of the method was 4.2% (n = 5) with a limit of detection (LOD) of 0.014 µM. A remarkable selectivity was achieved for tyramine detection in the presence of other biogenic amines, especially histamine. This methodology, based on the optical properties of Au(III)/tectomer hybrid coatings, is promising for its application in food quality control and smart food packaging.

Portable colorimetric enzymatic disposable biosensor for histamine and simultaneous histamine/tyramine determination using a smartphone.

Tyramine oxidase (TAO), peroxidase (HRP), and Amplex Red (AR) have been immobilized on cellulose to obtain disposable biosensors for the determination of histamine. During the enzymatic reaction, AR is oxidized and a pink spot is obtained. Using a smartphone and measuring the G (green) color coordinate, histamine can be determined in the presence of other biogenic amines (putrescine and cadaverine) in concentrations ranging from 2·10-5 M to 5·10-4 M with a 7.5·10-6 M limit of detection (LoD). Despite tyramine interference, experimental conditions are provided which allow rapid and simple histamine and simultaneous histamine/tyramine (semi)quantitative determination in mixtures. Finally, tyramine and histamine were determined in a tuna extract with good results (compared to the reference HPLC-MS method). The methodology can also be applied in solution allowing histamine (and simultaneous histamine/tyramine) determination with a lower LoD (1.8·10-7 M) and a similar selectivity.

Enzymatically mediated fluorescent copper nanocluster generation for tyramine determination.

This work details the enzymatic generation of fluorescence nanomaterials and the use of this optical signal as the analytical parameter for the quantification of the substrate. More specifically, fluorescent copper nanoclusters have been obtained during the enzymatic reaction of tyramine oxidase and tyramine in the presence of Cu(II); the fluorescence intensity being proportional to the concentration of tyramine. The nanoclusters obtained show fluorescence at 445 nm by being excited at 320 nm and have been characterized by TEM, EDX, and XPS. The formation mechanism has also been studied, suggesting that under the optimal conditions (0.1 M MES buffer and pH = 6), the formation of the nanoclusters is due to the reducing properties of the product of the enzymatic reaction (p-hydroxybenzaldehyde) in MES buffer. The method shows a linear relationship with the concentration of tyramine in the range from 1.0·10-5 to 2.5·10-4 M, a RSD of 3% (n = 5) and a LOD of 6.3·10-6 M. The method has been applied to the determination of tyramine in sausage with good results.

Visual simulations of presbyopic corrections through cataract opacification.

PURPOSE: To study the viability of visual simulation of presbyopic correction in patients with cataract and the effect and impact of the cataract on the perceived visual quality of the different simulated presbyopic corrections preoperatively and postoperatively. SETTING: San Carlos Clinical Hospital, Madrid, Spain. DESIGN: Observational, noninterventional, pilot study, early feasibility of the device being studied. METHODS: Cataract patients were tested preoperatively (n = 24) and postoperatively (n = 15) after bilateral implantation of monofocal intraocular lenses (IOLs). The degree of cataract was evaluated objectively with the objective scatter index (OSI). Visual acuity (VA) and perceived visual quality of natural scene images (Multifocal Acceptance Score) were measured before and after cataract surgery at far (4 m), intermediate (64 cm) and near distance (40 cm) with 4 binocular presbyopic corrections (single vision, bifocal, monovision and modified-monovision) simulated with a binocular Simultaneous Vision simulator based on temporal multiplexing. RESULTS: VA was significantly correlated with OSI ( r = -0.71, P < .0005), although the visual degradation at far for each correction was constant and not correlated with OSI. The visual benefit at near distance provided by the presbyopic correction was noticeable (23.3% ± 27.6% across corrections) for OSI <5. The individual perceptual scores were highly correlated preoperatively vs postoperatively ( r = 0.64, P < .0005) for all corrections and distances. CONCLUSIONS: Visual simulations of IOLs are an excellent tool to explore prospective postoperative vision. The high correlation in the perceptual scores pre- and post-cataract surgery demonstrates that SimVis Gekko can be used in cataractous patients to guide the selection of the optimal correction for a patient.

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.

Foveal and peripheral visual quality and accommodation with multifocal contact lenses.

Multifocal contact lenses are increasingly popular interventions for controlling myopia. This study presents the short-term effects of multifocal contact lenses on foveal and peripheral vision. The MiSight contact lenses designed to inhibit myopia progression and the 1-Day Acuvue Moist contact lenses designed for presbyopia were investigated. The MiSight produced similar foveal results to spectacles despite the increased astigmatism and coma. The MiSight also reduced the low-contrast resolution acuity in the periphery, despite no clear change in relative peripheral refraction. When compared with spectacles, Acuvue Moist decreased accommodative response and reduced foveal high- and low-contrast resolution acuity, whereas peripheral thresholds were more similar to those of spectacles. The most likely treatment property for myopia control by the MiSight is the contrast reduction in the peripheral visual field and the changed accommodation.

Selective generation of gold nanostructures mediated by flavo-enzymes to develop optical biosensors.

This paper explores, for the first time, the use of flavo-enzymes for the enzymatic generation of gold nanomaterials. It has been demonstrated that when the oxidation of glucose by GOx is carried out in the presence of Au(III), the in-situ formation of gold nanomaterials is observed. Moreover, depending on the experimental conditions, either nanoparticles (AuNPs) or nanoclusters (AuNCs) are better observed, whose spectroscopical properties can be related to the concentration of glucose. Working at pH 6, only AuNCs with fluorescence at 420 nm (λex=335 nm) are obtained (linear relationship from 6.0·10-5 M to 1.5·10-3 M glucose). However, when the enzymatic reaction is performed at pH 8, AuNPs (λmax=580 nm) are also obtained (linear relationship from 5.5·10-4 M to 2.0·10-3 M glucose). Mathematical equations describing the variation of fluorescence and absorbance values during the reaction have been proposed. The results obtained suggest that AuNCs are formed using GOx as nucleation seeds. Since AuNPs belong to the branched-type, it is suggested that they are obtained by AuNC coalescence. From these models the AuNP molar absorptivity per atom was obtained (2.0(±0.3)·103 M-1cm-1). Finally, the method has been applied to the determination of glucose in orange juice and human plasma samples. Comparing the results with the GOx/HRP/TMB method and a commercial glucometer, no significant differences (P=0.05) are obtained.

Solving Color Reproducibility between Digital Devices: A Robust Approach of Smartphones Color Management for Chemical (Bio)Sensors.

In the past twelve years, digital image colorimetry (DIC) on smartphones has acquired great importance as an alternative to the most common analytical techniques. This analysis method is based on fast, low-cost, and easily-accessible technology, which can provide quantitative information about an analyte through the color changes of a digital image. Despite the fact that DIC is very widespread, it is not exempt from a series of problems that are not fully resolved yet, such as variability of the measurements between smartphones, image format in which color information is stored, power distribution of the illuminant used for the measurements, among others. This article proposes a methodology for the standardization and correction of these problems using self-developed software, together with the use of a 3D printed light box. This methodology is applied to three different colorimetric analyses using different types and brands of smartphones, proving that comparable measurements between devices can be achieved. As color can be related to many target analytes, establishing this measurement methodology can lead to new control analysis applicable to diverse sectors such as alimentary, industrial, agrarian, or sanitary.