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To determine whether patient-customized paraxial eye models that do not rely on exact ray tracing and do not consider aberrations can accurately predict pseudophakic refraction.Bascom Palmer Eye Institute, Miami, Florida.Prospective study.Cataract surgery patients with and without a history of refractive surgery were included. Manifest refraction, corneal biometry, and extended-depth optical coherence tomography (OCT) imaging were performed at least 1 month postoperatively. Corneal and OCT biometry were used to create paraxial eye models. The pseudophakic refraction simulated using the eye model was compared with measured refraction to calculate prediction error.49 eyes of 33 patients were analyzed, of which 12 eyes from 9 patients had previous refractive surgery. In eyes without a history of refractive surgery, the mean prediction error was 0.08 ± 0.33 diopters (D), ranging from -0.56 to 0.79 D, and the mean absolute error was 0.27 ± 0.21 D. 31 eyes were within ±0.5 D, and 36 eyes were within ±0.75 D. In eyes with previous refractive surgery, the mean prediction error was -0.44 ± 0.58 D, ranging from -1.42 to 0.32 D, and the mean absolute error was 0.56 ± 0.46 D. 7 of 12 eyes were within ±0.5 D, 8 within ±0.75 D, and 10 within ±1 D. All eyes were within ±1.5 D.Accurate calculation of refraction in postcataract surgery patients can be performed using paraxial optics. Measurement uncertainties in ocular biometry are a primary source of residual prediction error.

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.

The mechanics of accommodation is a complex process that involves multiple intraocular ocular structures. Recent studies suggest that there is deformation of the sclera during accommodation that may also play a role in accommodation, influencing ciliary muscle contraction and contributing to the accommodative response. However, the type and magnitude of the deformations measured varies significantly across studies. We present high-resolution synchronous OCT measurements of the anterior sclera contour and thickness and lens thickness acquired in real-time during accommodative responses to 4D step stimuli. The lens thickness was used as an assessment of objective accommodation. No changes in nasal and temporal anterior scleral contour and scleral thickness were found during accommodation within the precision of our measurements. Our results demonstrate that there are no significant scleral deformations during accommodation.

19 pags., 9 figs., 5 tabs., 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., HORIZON EUROPE European Research Council (IMCUSTOMEYE H2020-ICT-2017 Ref. 779960;); European Research Council (SILKEYE H2020-ERC-571 2018-ADG Ref.833106); Ministerio de Ciencia e Innovación (PID2020-115191RB-I00); Narodowa Agencja Wymiany Akademickiej (ULAM 2020/1/00176); Fundacja narzecz Nauki Polskiej (MAB/2019/12); L’Oréal-UNESCO “For Women in Science”; Ministerio de Ciencia, Innovación y Universidades (IJC2018-037508-I, Juan de la Cierva-Incorporation); Research to Prevent Blindness (Bascom Palmer Eye Institute, Flaum Eye Institute); National Institutes of Health (NIE P30EY 001319); Unrestricted Funds Research to Prevent Blindness, NY; National Institutes of Health (R01EY021834); National Institutes of Health (P30EY014801); Florida Lions Eye Bank and Beauty of Sight Foundation; Hyderabad Eye Research Foundation.

To determine the effect of temperature on the accommodative response of non-human primate crystalline lenses during simulated accommodation.Eight lenses from 7 cynomolgus monkeys (Macaca fascicularis, ages: 4.5-7.3 years; post-mortem time: 17.0 ± 16.4 h) were mounted in a lens stretcher. Stretching experiments were performed on each lens at 24 °C (room temperature), then the tissue was warmed to 35 °C (intraocular temperature) and the stretching experiments were repeated. The lens diameter, thickness, anterior and posterior surface radii of curvature, optical power, and the stretching force (load) were measured at each stretch position and the linear optomechanical relationships were quantified: load-lens diameter, load-thickness, power-load, load-anterior radius, and load-posterior radius. The rate of change for each parameter was quantified by performing a linear regression. The slopes of the linear regressions were compared at the two temperatures using a paired sample t-test.The average changes in the lens with stretching at 24 °C and 35 °C were: 3.07 ± 0.17 and 2.58 ± 0.15 for load-lens diameter (g/mm), -2.38 ± 0.20 and -2.00 ± 0.32 for load-thickness (g/mm), -13.35 ± 1.21 and -13.75 ± 1.26 for power-load (D/g), 0.41 ± 0.10 and 0.34 ± 0.05 for load-anterior radius of curvature (g/mm), and 1.35 ± 0.24 and 1.31 ± 0.35 for load-posterior radius of curvature (g/mm), respectively. The changes in load-diameter and load-thickness with lens stretching were significantly different for the two temperatures.Temperature influences the change in lens shape observed during simulated accommodation in non-human primate lenses. These results suggest that lens stretching experiments and other optomechanical measurement techniques on ex vivo crystalline lenses be conducted at 35 °C and that the temperature of the tissue sample be documented and maintained constant to ensure repeatability.

The lens of the eye has a refractive index gradient that changes as the lens grows throughout life. These changes play a key role in the optics of the eye. Yet, the lens is generally simulated using a homogeneous model with an equivalent index that does not accurately represent the gradient. We present an analytical paraxial model of the gradient lens of the eye that gives the direct relation between refractive index distribution and paraxial characteristics. The model accurately simulates the changes in lens power with age and accommodation. It predicts that a decrease in equivalent index with age is associated with a flattening of the axial refractive index profile and that changes in lens power with accommodation are due primarily to changes in the axial variation of the iso-indicial curvature, consistent with Gullstrand’s intracapsular theory of accommodation. The iso-indicial curvature gradient causes a shift of the principal planes compared to the homogeneous equivalent model. This shift introduces a clinically significant error in eye models that implement a homogenous lens. Our gradient lens model can be used in eye models to better predict the optics of the eye and the changes with age and accommodation.

We have combined an anterior segment (AS) optical coherence tomography (OCT) system and a wavefront-based aberrometer with an approach that senses ocular wavefront aberrations using the OCT beam. Temporal interlacing of the OCT and aberrometer channels allows for OCT images and refractive error measurements to be acquired continuously and in real-time. The system measures refractive error with accuracy and precision comparable to that of clinical autorefractors. The proposed approach provides a compact modular design that is suitable for integrating OCT and wavefront-based autorefraction within the optical head of the ophthalmic surgical microscope for guiding cataract surgery or table-top devices for simultaneous autorefraction and ocular biometry.

It is well known that human crystalline lens shape, dimensions and optical properties change throughout life and influence whole eye refraction. However, it is not clear if lens properties are associated with other ocular parameters. The purpose of the present study was to investigate the relationship of corneal and external globe dimensions with adult lens diameter (LD), lens thickness (LT) and lens power (LP) in order to determine if external factors influence lens properties. Postmortem human eyes (n = 66, age = 20-78 years) were obtained from the Ramayamma International Eye Bank, Hyderabad, India. Globe antero-posterior length (GAPL) and mean (average of horizontal and vertical) diameters of cornea (MCD) and globe (MGD) were measured using digital calipers. Eyes were dissected to produce ocular structures that contain the lens maintained in its accommodating framework, including intact zonules, ciliary body and sections of sclera. Specimens were mounted in a mechanical lens stretching system. LD, LT and LP were measured using high magnification retro-illumination photography, slit illumination photography and Scheiner principle-based optical system respectively in the unstretched (accommodated) state. Relationships between external globe and corneal dimensions and LD, LT or LP were assessed by multiple regression analysis. Age (0.012 ± 0.003 mm/year; p

We acquired 1325 nm OCT images of the sclera and ciliary muscle of human subjects. The attenuation coefficients of the sclera and ciliary muscle were determined from a curve fit of the average intensity profile of about 100 A-lines in a region of interest after correction for the effect of beam geometry, using a single scattering model. The average scleral attenuation coefficient was 4.13 ± 1.42 mm-1 with an age-related decrease that was near the threshold for statistical significance (p = 0.053). The average ciliary muscle attenuation coefficient was 1.72 ± 0.88 mm-1, but this value may be an underestimation due to contributions from multiple scattering. Overall, the results suggest that inter-individual variations in scleral attenuation contribute to variability in the quality of transscleral OCT images of the ciliary muscle and the outcome of transscleral laser therapies.

In an effort to meet the need of imaging technology that reliably measure the dynamics of accommodation, we developed a swept source OCT system for imaging and biometry of the crystalline lens dynamics at high sampling rates (~100 Hz). Preliminary data suggests that high sampling rates improve detection of lens micro-fluctuations during accommodation and that sampling rates higher than 40 Hz might be needed to fully capture crystalline lens dynamics. Long term, the information acquired with the system will improve our understanding of the mechanism of accommodation and enable to design and evaluate new procedures to restore accommodation.

6 pags., 2 figs., 2 tabs., 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., This work was supported by the National Institutes of Health/National Eye Institute [Grants 2R01EY021834 and P30EY14801 (Center Grant)]; the Hyderabad Eye Research Foundation; Ministerio de Educacion y Ciencia, Spain (FIS2017- 84753-R), European Research Council (ERC-2018-AdG-833106) and IMCUSTOMEYE Ref. 779960 (H2020- ICT- 2017-1) to S. Marcos, and European Research Council (ERC) under European Union’s Horizon 2020 research and innovation programme H2020-MSCA COFUND-2015 FP-713694, MULTIPLY(AdC), CSIC ICoop Program, Florida Lions Eye Bank and the Beauty of Sight Foundation, an unrestricted grant from Research to Prevent Blindness to the Department of Ophthalmology, University of Miami and the Henri and Flore Lesieur Foundation (J-M. Parel).

There is a great need for accurate biometric data on human lenses. To meet this, a compact tabletop optical comparator, the minishadowgraph, was built for measuring isolated eye lens shape and dimensions while the lens was fully immersed in supporting medium. The instrument was based around a specially designed cell and an illumination system which permitted image recording in both sagittal and equatorial (coronal) directions. Data were acquired with a digital camera and analyzed using a specially written MATLAB program as well as by manual measurements in image analysis software. The possible effect of lens orientation and gravity on the dimensions was examined by measuring dimensions with anterior or posterior surfaces up and by measuring lenses with calipers after removal from the minishadowgraph cell. Dimensions, curvatures and shape factors were obtained for 134 fully accommodated lenses ranging in age from birth to 88 years postnatal. Of these, 41 were from donors aged under 20 years, ages which are generally of limited availability. Thickness and diameter showed the same age-related trends described in previous studies but, for the lenses measured in air, age-dependent differences were observed in thickness (-5 to 0%) and diameter (+5 to 0%), consistent with gravitational sag. Anterior and posterior radii of curvature of the central 3 or 6 mm, depending on lens diameter, increase with age, with the anterior increase greater than the posterior. The anterior surface shape of the neonatal lens is that of a prolate ellipse and the posterior, an oblate ellipse. Both surfaces become hyperbolic after age 20. The data presented here on dimensions, shape and sagging will be of great value in assessing age-related changes in the optical and mechanical performance of the lens. In particular, the comprehensive data set from donors aged under 20 years provides a unique and valuable insight to the changes in size and shape during the early dynamic growth period of the lens.

The mouse lens is frequently used both in vivo and ex vivo in ophthalmic research to model conditions affecting the human lens, such as presbyopia. The mouse lens has a delicate structure which is prone to damage and biomechanical changes both before and after extraction from the whole globe. When not properly controlled for, these changes can confound the biomechanical analysis of mouse lenses. In this study, atomic force microscopy microindentation was used to assess changes in the Young's Modulus of Elasticity of the mouse lens as a function of mouse age and postmortem time. Old mouse lenses measured immediately postmortem were significantly stiffer than young mouse lenses (p = 0.028). However, after 18 h of incubation, there was no measurable difference in lens stiffness between old and young mouse lenses (p = 0.997). This demonstrates the need for careful experimental control in experiments using the mouse lens, especially regarding postmortem time.

Anatomical changes of the growing crystalline lens influence its refractive development, including power and spherical aberration. We have recently developed a new instrument that characterizes both the optical and biometric properties of the lens in-vitro by merging Ray-Tracing Aberrometry (RTA) with three-dimensional OCT imaging. In this abstract, we describe the application of the RTA to the measurement of lens spherical aberration. Experiments were performed on 54 isolated human lenses (age: 0.25 to 56 years). The system was programmed to sequentially deliver the probing beam through the lens using a raster scan pattern of 13 × 13 transversal positions spaced 0.5 mm apart. Exit rays were imaged after exiting the tissue chamber at 9 different axial positions (ΔZ = 0 mm to 8 mm) in 1 mm intervals. A total of 1,521 spot images were acquired per lens. All data was automatically analyzed using custom software we developed in MATLAB. Exit ray slopes over a 6 mm pupil were used to determine Zernike wavefront coefficients up to the sixth order. The 4th order Zernike coefficient Z[4,0] was used to measure primary spherical aberration (SA). The results suggest that spherical aberration of the growing lens becomes more negative before adulthood and less negative after around age 30. The data is consistent with results from in-vivo studies that suggest the lens spherical aberration becomes less negative in older lenses (>30 years).

13 pags., 7 figs., 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., European Research Council (ERC) under European Union’s Horizon 2020 research and innovation programme (H2020-MSCA COFUND-2015 FP-713694, MULTIPLY); Spanish government (FIS2014-56643-R, FIS2017-84753-R); European Research Council under the European Union’s Seventh Framework programme (ERC-2011-AdG-2940); National Eye Institute (R01EY021834; F31EY021444); Ruth L. Kirschstein National Research Service Award Individual Pre-doctoral Fellowship (P30EY14801 Center Core Grant); the Florida Lions Eye Bank and Beauty of Sight Foundation; the Henri and Flore Lesieur Foundation.

Purpose To characterize the peripheral defocus of isolated human crystalline lenses and its age dependence. Methods Data were acquired on 116 isolated lenses from 99 human eyes (age range, 0.03-61 years; postmortem time, 40.1 ± 21.4 hours). Lenses were placed in a custom-built combined laser ray tracing and optical coherence tomography system that measures the slopes of rays refracted through the lens for on-axis and off-axis incidence angles. Ray slopes were measured by recording spot patterns as a function of axial position with an imaging sensor mounted on a positioning stage below the tissue chamber. Delivery angles ranged from -30° to +30° in 5° increments using a 6 mm × 6 mm raster scan with 0.5-mm spacing. Lens power at each angle was calculated by finding the axial position that minimizes the root-mean-square size of the spot pattern formed by the 49 central rays, corresponding to a 3-mm zone on-axis. The age dependence of the on-axis and off-axis optical power and the relative peripheral defocus (difference between off-axis and on-axis power) of lenses were quantified. Results At all angles, lens power decreased significantly with age. Lens power increased with increasing delivery angle for all lenses, corresponding to a shift toward myopic peripheral defocus. There was a statistically significant decrease in the lens peripheral defocus with age. Conclusions The isolated human lens power increases with increasing field angle. The lens relative peripheral defocus decreases with age, which may contribute to the age-related changes of ocular peripheral defocus during refractive development.

Rose bengal photodynamic antimicrobial therapy (RB-PDAT) treats corneal infection by activating rose bengal (RB) with green light to produce singlet oxygen (1O2). Singlet oxygen dosimetry can help optimize treatment parameters. We present a 1O2 dosimeter for detection of 1O2 generated during experimental RB-PDAT. The system uses a 520 nm laser and an InGaAs photoreceiver with bandpass filters to detect 1O2 luminescence during irradiation. The system was validated in RB solutions and ex vivo in human donor eyes. The results demonstrate the feasibility of 1O2 dosimetry in an experimental model of RB-PDAT in the cornea.

The Ocular Photosensitivity Analyzer (OPA), a new automated instrument to quantify the visual photosensitivity thresholds (VPT) in healthy and light sensitive subjects, is described. The OPA generates light stimuli of varying intensities utilizing unequal ascending and descending steps to yield the VPT. The performance of the OPA was evaluated in healthy subjects, as well as light sensitive subjects with achromatopsia or traumatic brain injury (TBI). VPT in healthy, achromatopsia, and TBI subjects were 3.2 ± 0.6 log lux, 0.5 ± 0.5 log lux, and 0.4 ± 0.6 log lux, respectively. Light sensitive subjects manifested significantly lower VPT compared to healthy subjects. Longitudinal analysis revealed that the OPA reliably measured VPT in healthy subjects.

We present a new in vitro instrument for measuring shape and wavefront aberrations of the primate crystalline lens, both on- and off-axis, while simulating accommodation with a motorized lens stretching system. The instrument merges spectral domain optical coherence tomography (SD-OCT) imaging and ray tracing aberrometry using an approach that senses wavefront aberrations of the lens with the OCT probing beam. Accuracy and repeatability of aberration measurements were quantified. Preliminary experiments on two human and four cynomolgus monkey lenses demonstrate the ability of the system to measure the lens shape, spherical aberration and peripheral defocus, and their changes during simulated accommodation.

Purpose To characterize the peripheral defocus of the monkey crystalline lens and its changes with accommodation. Methods Experiments were performed on 15 lenses from 11 cynomolgus monkey eyes (age: 3.8-12.4 years, postmortem time: 33.5 ± 15.3 hours). The tissue was mounted in a motorized lens stretcher to allow for measurements of the lens in the accommodated (unstretched) and unaccommodated (stretched) states. A custom-built combined laser ray tracing and optical coherence tomography system was used to measure the paraxial on-axis and off-axis lens power for delivery angles ranging from -20° to +20° (in air). For each delivery angle, peripheral defocus was quantified as the difference between paraxial off-axis and on-axis power. The peripheral defocus of the lens was compared in the unstretched and stretched states. Results On average, the paraxial on-axis lens power was 52.0 ± 3.4 D in the unstretched state and 32.5 ± 5.1 D in the stretched state. In both states, the lens power increased with increasing delivery angle. From 0° to +20°, the relative peripheral lens power increased by 10.7 ± 1.4 D in the unstretched state and 7.5 ± 1.6 D in the stretched state. The change in field curvature with accommodation was statistically significant (P < 0.001), indicating that the unstretched (accommodated) lens has greater curvature or relative peripheral power. Conclusions The cynomolgus monkey lens has significant accommodation-dependent curvature of field, which suggests that the lens asserts a significant contribution to the peripheral optical performance of the eye that also varies with the state of accommodation.

Purpose: To objectively quantify dynamic changes in lens shape during accommodation using two-dimensional OCT images Methods: In-vivo responses to an accommodative step stimulus of three subjects (aged 22, 39, and 45) were captured using a custom-made extended-depth SD-OCT system operating at 840 nm following an IRB-approved protocol (Ruggeri et al. 2012). Subjects focused on a visual accommodation target designed to produce an adjustable step stimulus of accommodation. Accommodative responses to 2-D and 4-D stimuli were captured ~1.5s before and ~4.5s after stimulation. Lens thickness, anterior curvature, and posterior curvature were measured using a newly-developed algorithm (validated using a calibration sphere). Dynamic changes in lens thickness and curvature were then fitted with an exponential model to produce time dependent constants. Results: All calibration OCT images were automatically analyzed in under 2 seconds. A radius of 7.793mm ± 0.051mm was calculated resulting in a difference of 2.4μm from the reported nominal value of the calibration sphere. Anterior lens radius decreased over time in all subjects. Radius of the posterior lens experienced a slight increase for all subjects. Conclusion: This study demonstrates the feasibility of quantifying the dynamic changes in lens curvature and thickness during accommodation using extended-depth OCT combined with a step accommodation stimulus and an automated segmentation algorithm.

A non-linear isotropic finite element (FE) model of a 29-year-old human crystalline lens was constructed to study the effects of various geometrical parameters on lens accommodation.The model simulates dis-accommodation by stretching of the lens and predicts the change in surface profiles of the lens capsule, cortex and nucleus at select states of stretching/accommodation. Multiple regression analysis (MRA) is used to develop a stretch-dependent mathematical model relating the lens sagittal height to the radial position of the lens surface as a function of dis-accommodative stretch. A load analysis is performed to compare the finite element results to empirical results from lens stretcher studies. Using the predicted geometrical changes, the optical response of the whole eye during accommodation was analysed by ray-tracing.Aspects of lens shape change relative to stretch were evaluated, including change in diameter, central thickness and accommodation. Maximum accommodation achieved was 10.29 D. From the multiple regression analysis, the stretch-dependent mathematical model of the lens shape related lens curvatures as a function of lens ciliary stretch well (maximum mean-square residual error 2.5 × 10(-3 ) μm, p0.001). The results are compared with those from in vitro studies.The finite element and ray-tracing predictions are consistent with Ex Vivo Accommodation Simulator (EVAS) studies in terms of load and power change versus change in thickness. The mathematical stretch-dependent model of accommodation presented may have utility in investigating lens behaviour at states other than the relaxed or fully accommodated states.

Purpose To determine the role of anterior and posterior zonular tension on the optomechanical lens response during accommodation simulation. Methods Ten eyes from nine hamadryas baboons (4.9 ± 0.7 years) and 20 eyes from 18 cynomolgus monkeys (5.4 ± 0.3 years) were dissected, leaving the lens, zonules, ciliary body, hyaloid membrane, anterior vitreous, and a segmented scleral rim intact. The lens preparation was mounted in a lens stretcher, and the outer scleral shell was displaced radially in a stepwise fashion. The load, lens, and ciliary body diameters, lens power, lens thickness, and the anterior and posterior radius of curvature were measured during stretching. The zonular fibers attached to either the posterior or anterior lens surface were then carefully transected and the experiment was repeated. Zonular transection was confirmed in four eyes via laser scanning confocal microscopy after immunostaining. The effect of zonular transection on the tissue response to stretching was quantified. Results Without anterior zonules, 48% and 97% of the changes in anterior and posterior radii are retained. Without posterior zonules, 81% and 67% of the changes in anterior and posterior radii are retained. The changes in lens shape were reduced after transecting either the anterior or posterior zonules; however, both surfaces still changed shape. Conclusions While either the anterior or posterior zonules alone are capable of changing the shape of both lens surfaces, the anterior zonules have a greater effect on the anterior lens surface, and the posterior zonules have a greater effect on the posterior lens surface.

PURPOSE To evaluate the capability of a novel, coaligned focused ultrasound and phase-sensitive optical coherence elastography (US-OCE) system to assess age-related changes in biomechanical properties of the crystalline lens in situ. METHODS Low-amplitude elastic deformations in young and mature rabbit lenses were measured by an US-OCE system consisting of a spectral-domain optical coherence tomography (OCT) system coaligned with a focused ultrasound system used to produce a transient force on the lens surface. Uniaxial compressional tests were used to validate the OCE data. RESULTS The OCE measurements showed that the maximum displacements of the young rabbit lenses were significantly larger than those of the mature lenses, indicating a gradual increase of the lens stiffness with age. Temporal analyses of the displacements also demonstrate a similar trend of elastic properties in these lenses. The stress-strain measurements using uniaxial mechanical tests confirmed the results obtained by the US-OCE system. CONCLUSIONS The results demonstrate that the US-OCE system can be used for noninvasive analysis and quantification of lens biomechanical properties in situ and possibly in vivo.

Optical coherence tomography (OCT) offers new options for imaging the ciliary muscle allowing direct in vivo visualization. However, variation in image quality along the length of the muscle prevents accurate delineation and quantification of the muscle. Quantitative analyses of the muscle are accompanied by variability in segmentation between examiners and between sessions for the same examiner. In processes such as accommodation where changes in muscle thickness may be tens of microns- the equivalent of a small number of image pixels, differences in segmentation can influence the magnitude and potentially the direction of thickness change. A detailed analysis of variability in ciliary muscle thickness measurements was performed to serve as a benchmark for the extent of this variability in studies on the ciliary muscle. Variation between sessions and examiners were found to be insignificant but the magnitude of variation should be considered when interpreting ciliary muscle results.

Purpose: To determine the dynamic interaction between ciliary muscle and lens during accommodation and disaccommodation through synchronous imaging of ciliary muscle and lens response to pulse stimulus Methods: The ciliary muscle and lens were imaged simultaneously in a 33 year old subject responding to a 4D pulse stimulus (accommodative stimulus at 1.7 s, disaccommodative stimulus at 7.7 s) using an existing imaging system (Ruggeri et al, 2016) consisting of an Anterior Segment Optical Coherence Tomography system, Ciliary Muscle Optical Coherence Tomography system, and custom-built accommodation module. OCT images were recorded at an effective frame rate of 13.0 frames per second for a total scan time of 11.5 s. An automated segmentation algorithm was applied to images of the anterior segment to detect the boundaries of the cornea and lens, from which lens thickness was extracted. Segmentation of the ciliary muscle was performed manually and then corrected for distortion due to refraction of the beam to obtain measurements of thicknesses at the apex and fixed distances from the scleral spur. Results: The dynamic biometric response to a pulse stimulus at 4D was determined for both the ciliary muscle and lens, suggesting the ciliary muscle and lens interact differently in accommodation and disaccommodation. Conclusions: The study introduces new data and analyses of the ciliary muscle and lens interaction during a complete accommodative response from the relaxed to the accommodated state and back, providing insight into the interplay between individual elements in the accommodative system and how their relationships may change with age.

Age-related changes in the crystalline lens shape and refractive index gradient produce changes in dioptric power and high-order aberrations that influence the optics of the whole eye and contribute to a decrease in overall visual quality. Despite their key role, the changes in lens shape and refractive index gradient with age and accommodation and their effects on high-order aberrations are still not well understood. The goal of this project was to develop a combined laser ray tracing (LRT) and optical coherence tomography (OCT) system to measure high-order aberrations, shape and refractive index gradient in non-human primate and human lenses. A miniature motorized lens stretching system was built to enable imaging and aberrometry of the lens during simulated accommodation. A positioning system was also built to enable on- and off-axis OCT imaging and aberrometry for characterization of the peripheral defocus of the lens. We demonstrated the capability of the LRT-OCT system to produce OCT images and aberration measurements of crystalline lens with age and accommodation in vitro. In future work, the information acquired with the LRT-OCT system will be used to develop an accurate age-dependent lens model to predict the role of the lens in the development of refractive error and aberrations of the whole eye.

The lens equivalent refractive index (RI) is commonly used in calculations of crystalline lens power. However, accurate determination of the equivalent RI in vivo is challenging due to the need of multiple measurements with different ocular biometry devices. A custom extended-depth Spectral Domain-OCT system was utilized to provide measurements of corneal and lens surface curvatures and all intraocular distances required for determination of the lens equivalent RI. Ocular biometry and refraction were input into a computational model eye from which the equivalent RI was calculated. Results derived from human subjects of a wide age range show a decrease in RI with age and demonstrate the capability of in vivo measurements of the equivalent RI with extended-depth OCT.

Hand-held wide-field contact color fundus photography is currently the standard method to acquire diagnostic images of children during examination under anesthesia and in the neonatal intensive care unit. The recent development of portable non-contact hand-held OCT retinal imaging systems has proved that OCT is of tremendous help to complement fundus photography in the management of pediatric patients. Currently, there is no commercial or research system that combines color wide-field digital fundus and OCT imaging in a contact-fashion. The contact of the probe with the cornea has the advantages of reducing motion experienced by the photographer during the imaging and providing fundus and OCT images with wider field of view that includes the periphery of the retina. In this study we produce proof of concept for a contact-type hand-held unit for simultaneous color fundus and OCT live view of the retina of pediatric patients. The front piece of the hand-held unit consists of a contact ophthalmoscopy lens integrating a circular light guide that was recovered from a digital fundus camera for pediatric imaging. The custom-made rear piece consists of the optics to: 1) fold the visible aerial image of the fundus generated by the ophthalmoscopy lens on a miniaturized level board digital color camera; 2) conjugate the eye pupil to the galvanometric scanning mirrors of an OCT delivery system. Wide-field color fundus and OCT images were simultaneously obtained in an eye model and sequentially obtained on the eye of a conscious 25 year-old human subject with healthy retina.

The purpose of this project is to design and evaluate a system that will enable objective assessment of the optical accommodative response in real-time while acquiring axial biometric information. The system combines three sub-systems which were integrated and mounted on a joystick x-y-z adjustable modified slit-lamp base to facilitate alignment and data acquisition: (1) a Shack-Hartmann wavefront sensor for dynamic refraction measurement, provided software calculates sphere, cylinder and axis values, (2) an extended-depth Optical Coherence Tomography (OCT) system using an optical switch records high-resolution cross-sectional images across the length of the eye, from which, dynamic axial biometry (corneal thickness, anterior chamber depth, crystalline lens thickness and vitreous depth) can be extracted, and (3) a modified dual-channel accommodation stimulus unit based on the Badal optometer for providing a step change in accommodative stimulus. The prototypal system is capable of taking simultaneous measurements of both the optical and the mechanical response of lens accommodation. These measurements can provide insight into correlating changes in lens shape with changes in lens power and ocular refraction and ultimately provide a more comprehensive understanding of accommodation, presbyopia and an objective assessment of presbyopia correction techniques.

Two SD-OCT systems and a dual channel accommodation target were combined and precisely synchronized to simultaneously image the anterior segment and the ciliary muscle during dynamic accommodation. The imaging system simultaneously generates two synchronized OCT image sequences of the anterior segment and ciliary muscle with an imaging speed of 13 frames per second. The system was used to acquire OCT image sequences of a non-presbyopic and a pre-presbyopic subject accommodating in response to step changes in vergence. The image sequences were processed to extract dynamic morphological data from the crystalline lens and the ciliary muscle. The synchronization between the OCT systems allowed the precise correlation of anatomical changes occurring in the crystalline lens and ciliary muscle at identical time points during accommodation. To describe the dynamic interaction between the crystalline lens and ciliary muscle, we introduce accommodation state diagrams that display the relation between anatomical changes occurring in the accommodating crystalline lens and ciliary muscle.

Functionalised siloxane macromonomers, with properties designed for application as an injectable, in situ curable accommodating intraocular lens (A-IOL), were prepared via re-equilibration of a phenyl group-containing polysiloxane of very high molecular weight with octamethylcyclotetrasiloxane (D₄) and 2,4,6,8-tetra(n-propyl-3-methacrylate)-2,4,6,8-tetramethyl-cyclotetrasiloxane (D₄(AM)) in toluene using trifluoromethanesulfonic acid as a catalyst. Hexaethyldisiloxane was used as an end group to control the molecular weight of the polymer. The generated polymers had a consistency suitable for injection into the empty lens capsule. The polymers contained a low ratio of polymerisable groups so that, in the presence of a photo-initiator, they could be cured on demand in situ within 5 min under irradiation of blue light to form an intraocular lens within the lens capsule. All resulting polysiloxane soft gels had a low elastic modulus and thus should be able to restore accommodation. The pre-cure viscosity and post-cure modulus of the generated polysiloxanes were controlled by the end group and D₄(AM) concentrations respectively in the re-equilibration reactions. The refractive index could be precisely controlled by adjusting the aromatic ratio in the polymer to suit such application as an artificial lens. Lens stretching experiments with both human and non-human primate cadaver lenses of different ages refilled with polysiloxane polymers provided a significant increase in amplitude of accommodation (up to 4 D more than that of the respective natural lens). Both in vitro cytotoxicity study using L929 cell lines and in vivo biocompatibility study in rabbit models demonstrated the non-cytotoxicity and ocular biocompatibility of the polymer.

An optical switch was implemented in the reference arm of an extended depth SD-OCT system to sequentially acquire OCT images at different depths into the eye ranging from the cornea to the retina. A custom-made accommodation module was coupled with the delivery of the OCT system to provide controlled step stimuli of accommodation and disaccommodation that preserve ocular alignment. The changes in the lens shape were imaged and ocular distances were dynamically measured during accommodation and disaccommodation. The system is capable of dynamic in vivo imaging of the entire anterior segment and eye-length measurement during accommodation in real-time.