Vision with spatial light modulator simulating multifocal contact lenses in an adaptive optics system.

Visual simulators are useful tools to provide patients experience of multifocal vision prior to treatment. In this study, commercially available center-near aspheric multifocal contact lenses (MCLs) of low, medium, and high additions were mapped on a spatial light modulator (SLM) and validated on a bench. Through focus visual acuity (TFVA) was measured in subjects through the SLM and real MCLs on the eye. A correlation metric revealed statistically significant shape similarity between TFVA curves with real and simulated MCLs. A Bland-Altman analysis showed differences within confidence intervals of ±0.01 logMAR for LowAdd/MediumAdd and ±0.06 logMAR for HighAdd. Visual performance with simulated MCLs outperformed real MCLs by ∼20%. In conclusion, SLM captures the profile of center-near MCLs and reproduces vision with real MCLs, revealing that the MCL profile and its interactions with the eye's optics (and not fitting aspects) account for the majority of the contributions to visual performance with MCLs.


Introduction
Multifocal contact lenses (MCL) are known solutions for correcting presbyopia, an age-related eye condition by which the crystalline lens loses its ability to dynamically focus [1]. In addition, MCLs have shown promising results in controlling myopia progression [2][3][4].
MCLs work under the principle of simultaneous vision, i.e., simultaneous projection of an image focused at far and an image focused at near. Presbyopes gain intermediate/near vision at the expense of some optical degradation at far [1,[5][6][7], and center-near, center-distance and concentric alternating-zone designs of MCLs exist in the market for presbyopia. The way MCLs work in myopes to slow down eye growth is not well understood, and may rely on reducing hyperopic defocus in the periphery or on decreasing accommodative lag [8,9]. The MCLs used for slowing myopia progression are generally center-distance or alternating center-near and distance zones [10].
In a recent study by our group [11], we studied the visual performance with center-near MCLs on eye in two age groups (young myopes and presbyopes) in the presence and absence of accommodation. We found that the multifocal visual performance compromise at far vision is in general compensated by the benefit of near vision both in presbyopic subjects without accommodation, and in accommodating young myopic subjects [11].
There are an increasing number of MCL designs commercially available which differ primarily in their power profile. Some designs show relatively abrupt changes between near and far while others have aspheric smooth surfaces, aimed at increasing the eye's depth of focus rather than producing two distinct foci. Designs also differ in the distributions and number of pupillary zones devoted for far and near [1,5]. Some studies have attempted to understand the success of the MCLs with respect to visual performance in different populations, the effect of added are several assumptions implicit in representing MCLs in terms of phase mapping, which may include potential discrepancies between the theoretical power profile and that of the manufactured lens, conformity of the MCL to the underlying cornea, decentration of the lens and shift between the corneal and pupil plane.
In this study, we tested, for the first time to our knowledge, the accuracy of a phase map representation of a commercially available MCL design using a SLM (PLUTO-VIS; Holoeye Photonics AG, Germany) in an AO visual simulator. This approach maintained the natural interactions between the subject's aberrations and those of the lens designs. In particular, we evaluated TF visual performance (TF visual acuity) with real MCLs on eye and the same designs (center-near aspheric MCLs of three different magnitudes of addition (low/medium/high) simulated in an AO visual simulator, in the same subjects. A comparison of the real and simulated TF curves allowed assessment of the SLM's ability to simulate the MCLs. In a previous study [21] we had used the SimVis visual simulator to simulate the multifocal lenses of different additions. In the current study we are using a SLM, which is the core technology of several laboratory-based visual simulators, and to our knowledge, one commercial visual simulator [34]. The study therefore supports the use of SLM-based simulators to mimic MCLs (at least with monochromatic stimuli) and the phase map representation of MCLs, also used as an intermediate step in other types of simulators such as SimVis.

Methods
TF optical performance of the three simulated MCLs was tested on bench. Through focus Visual Acuity (TFVA) was measured under cycloplegia and a fixed pupil diameter (5-mm pupil) with the simulated MCLs and with the real MCLs on eye. We selected 5-mm pupils as this pupil diameter guarantees that there was both near and far vision contributions to the retinal image. All patients were measured with three MCL additions (low, medium and high).

Subjects
A total of 7 subjects participated in the study, with ages ranging from 24 to 55 years old, spherical errors from -4.00D to -1.50 D, and astigmatism less than 0.75 D. Table 1 shows the individual patients' profiles. All the subjects except S6 and S7 were habitual contact lens wearers. A contact lens settling time of 10-15 minutes was given to all subjects to ensure proper fitting and comfort prior to starting the measurements with each MCL. The study protocols met the tenets of the Declaration of Helsinki, and had been approved by the CSIC Institutional Review Boards. All participants were informed about the study and experimental procedures and signed informed consent waivers prior to any study procedures. The IRB assigned project reference number is 080/2016.

Multifocal contact lenses
The MCLs (MCLs, 1-Day Acuvue Moist Multifocal, Johnson and Johnson Vision Care) used in this study were soft, daily disposable, and had a center-near aspheric profile (higher plus power is in the central part and decreases progressively towards the periphery), base curve of 8.4 mm and diameter of 14.3 mm, and were made out of Etafilcon A and with 58% water content [21,35] . In this study, center-near MCLs of three different additions (low, medium and high) were investigated. Potential differences in MCL performance associated to lens base power (i.e., lens thickness and central near zone diameter) were eliminated by having all patients wear -2 D for far (with the residual refractive error corrected using the Badal Optometer), and with three different additions Low (+1.25D), Medium (+1.75D) and High (+2.5D).

Adaptive optics visual simulator
The experiment was performed with a custom-developed AO system at the Visual Optics and Biophotonics Lab (Institute of Optics, Spanish National Research Council, Madrid, Spain), described in detail in previous publications [20,23,26]. In this study, the MCLs were mapped on a SLM. The current configuration of the AO system consists of 8 channels (described in previous publications [20,22,26]), 6 of which were used for the purposes of this study:(1) The Illumination channel, provided with a polychromatic supercontinuum laser source (SCLS, SC400 femtopower 1060 supercontinuum laser; Fianium Ltd, United Kingdom) combined with a dual acoustic-optic tunable filter (AOTF) module (Gooch & Housego, United Kingdom). A visible wavelength (555 nm) was chosen to illuminate the visual stimuli and an infrared wavelength (827 nm) was chosen for the illumination of the retina to obtain aberration measurements. (2) The AO channel, consisting of a Hartmann-Shack wavefront sensor (microlenses array 40×32, 3.6 mm effective diameter, centered at 1062 nm; HASO 32 OEM, Imagine Eyes, France) and the electromagnetic deformable mirror (DM) (52 actuators, 15-mm effective diameter, 50-µm stroke; MIRAO, Imagine Eyes, France) to measure and correct the high order aberrations (HOAs), respectively. In this study the DM and HS were used only to correct the aberrations of the system and to measure subjects' aberrations. Monitoring-Channel, consisting of a ring of infrared LEDs and a camera conjugated to the eye's pupil which was used to align the subject's eyes to the optical axis of the system and to monitor the pupil position throughout the experiment. (6) The Badal optometer channel, for correcting the residual defocus of the patient and to change defocus in the TF measurements.
All optoelectronic elements of the system (SCLS main source, Badal system, retinal image camera, pupil camera, Hartmann-Shack wavefront sensor, deformable mirror and Spatial Light Modulator) were automatically controlled and synchronized using custom-built software programmed in Visual C++ and C# (Microsoft, USA) and MATLAB (MathWorks, USA). The custom-developed routines made use of the manufactureŕs Software Development Kit for Hartmann-Shack centroid detection and wave aberration polynomial fitting.
Subjects were stabilized using a dental impression and were aligned to the system (using an x-y-z stage moving a bite bar) using the line of sight as a reference, while the natural pupil is viewed on the monitor. To ensure proper pupil diameter during the measurements, a 5-mm artificial pupil was placed in a conjugate pupil plane. Figure 1 shows the phase map of the three MCLs generated for the SLM. MATLAB routines were used to numerically simulate the designs, which were later programmed in a reflective phase-only LCoS-SLM following the same protocols as   [22]. A wrapping process [19] was applied to the phase patterns to achieve a maximum phase difference of 2π defined by the calibration of the SLM. The generated pattern is a grey-scale image, where each level of grey corresponds to a certain phase difference between 0 and 2π. Images were generated for a 5-mm pupil at the conjugated pupil plane where the SLM was placed. Calibration of the SLM was performed following the procedures indicated by the manufacturer for a wavelength of 555 nm. The distance power of the MCL phase maps was set to 0D.

On bench through focus optical quality
TF optical quality through the SLM simulated MCLs was evaluated on bench in the system, using 1-pass TF images of an E-letter (0.86 logMAR, 29arc min) optotype displayed in the DMD imaged on an artificial eye, consisting of a 50-mm focal length achromat and a CMOS sensor (DCC1240C -High-Sensitivity USB 2.0 CMOS Camera, 1280 × 1024, Global Shutter, Color Sensor, Thorlabs GmbH, Germany) acting as a "retina", as described earlier [22]. The stimuli were illuminated with 555-nm light coming from the SCLS (similarly to the measurements in patients). In all measurements, focus shifts were achieved by moving the Badal optometer from +1D to -4.5D in 0.25 steps.

Experimental procedure in subjects
Measurements in subject's were performed monocularly (dominant eye -determined by Miles test) with the natural aberrations of the subjects uncorrected, in a darkened room (20 cd/m 2 ) under cycloplegia with 1% Tropicamide (2 drops prior to the experiment, and repeated every hour). The experiment started after 20 min of cycloplegia. The non-measured eye was covered with a patch throughout the experiment. Subjects were aligned to the system by centering the eye's pupil (imaged in the pupil monitoring channel) to the optical axis of the instrument. Following centration, the subject was asked to adjust the Badal system position to achieve the best focus for far vision using a Maltese cross, starting with positive defocus values relative to the subject's expected best focus. The focus setting was repeated multiple times and the average of at least 5 settings was defined as the zero-defocus setting. This procedure was repeated for every condition tested (LowAdd/MediumAdd/HighAdd and NoLens), with both simulated and real MCLs.
TFVA (see Section 2.7) was measured in 7 different conditions, split into two sessions. Session 1: NoLens (control), LowAdd Real MCL; MediumAdd Real MCL; High Add Real MCL, and Session 2: NoLens (control), LowAdd SLM simulation; MediumAdd SLM simulation; HighAdd SLM simulation. A settling time of 10-15 min was given every time that a MCL was placed on eye. The MCLs fitting and centration was checked in the slit lamp at the start of each condition. The duration of Session 1 and 2 was approximately 3 and 4.5 hours, respectively. Each session was performed on two different days.

Through focus visual acuity (TFVA)
High contrast VA was measured for a fixed defocus range from -3D to +1D in 0.5 steps, shifted using a Badal optometer. VA was measured using an 8-Alternative Forced Choice (8AFC) [36] procedure with Tumbling E letters (Black E-letter on a green background at 555 nm presented in the DMD display) and QUEST (Quick Estimation by Sequential Testing) algorithm programmed with the Psych toolbox package [37][38][39] to calculate the sequence of the presented stimulus (letter size and orientation) in the test following the subject's response. Subjects had to determine the orientation of the E-letter, and the size of the stimulus in the subsequent presentation changed depending on the subject's response using a quaternion estimation algorithm. The QUEST routine for each VA measurement consisted of 35 trails, where the threshold criterion was set to 75%. The threshold VA measurement, was estimated as the average of the 10 last stimulus values. VA was expressed in terms of logMAR acuity (log MAR = -log 10 [decimal acuity]) [40].

Data analysis
For the on-bench optical quality experiment (TF E-letter imaged in the artificial eye), the image quality metric was obtained as the image correlation coefficient between the E-letter obtained for a given condition (MCL and all focus positions) and the image of the E-letter with NoLens (monofocal at best focus).
For measurements in patients, TFVA curves were compared between the real and SLM simulated MCLs. The following statistical analyses were performed (1) The Shapiro-Wilk normality test was performed between the two groups (real MCLs & simulated MCLs) (2) Non-parametric tests were done to compare individual conditions between the real and simulated MCLs (3) Intraclass correlation coefficients were done to analyze the correlation between SLM vs real MCLs. (4) Shape similarity of the TF curves obtained as the cross -correlation of the SLM and real MCL TFVA curves. Statistical analysis was performed with SPSS software Statistics 24.0 (IBM, United States) to test differences across results with the SLM simulated and real MCLs. Additionally, (1) RMS difference of the linearly interpolated TF curves (SLM vs real MCLs), in a 4-D range; (2) Bland-Altman analysis (SLM vs real MCLs) was done. D. An increase in the depth-of-focus with increasing additions can be qualitatively observed in the series of images. Figure 2 B shows the TF optical quality metric (image correlation) estimated from those images. The maximum image quality correlation at best focus was 0.99, 0.93 and 0.87 for LowAdd, MediumAdd and HighAdd MCLs, respectively. At -0.25 D from the best focus the image quality dropped by 28.9%,18.4%, and 6.4% for LowAdd, MediumAdd and HighAdd MCLs, respectively. Along with the slight decrease in image quality at best focus, and curve broadening, a negative shift of the best-focus peak is observed with increasing near addition.  Figure 3 shows the TF logMAR VA with the simulated (dashed lines) and real MCLs (solid lines), for all three additions (LowAdd, first column, orange; MediumAdd, second column, green; HighAdd, third column, purple) and for all subjects, when measured with a fixed pupil diameter (5 mm). The black bars show the differences between real and simulated MCLs at each focus position.

Through focus visual performance real and simulated MCLs-individual data
The average magnitude difference between real and simulated MCLs in logMAR at best focus is -0.01, -0.07, and 0.06 logMAR units for LowAdd, MediumAdd and HighAdd MCLs, respectively. As individual MCLs, the median of the differences between real and simulated MCLs are -0.048 with 95% CI [-0.078, -0.017], -0.049 with 95% CI [-0.080, -0.014], -0.033 with 95% CI [-0.069, 0.000] for LowAdd, MediumAdd and HighAdd respectively. The average Simulated-Real difference (with sign) was negative (-0.04 ± 0.01, -0.03 ± 0.01, and -0.03 ± 0.04, for LowAdd, MediumAdd and HighAdd MCLs respectively), indicating a slightly better average performance with the simulated MCLs in comparison with the real MCLs. Figure 4 shows the shape similarity metric (rho) comparing the real MCLs on eye with the simulated MCLs mapped on the SLM for all subjects. The average shape similarity metric was k=0, rho = 0.889 ± 0.03, k=0, rho=0.825 ± 0.05 and k=0, rho=0.651 ± 0.08 (average rho across individual subjects) for LowAdd, MediumAdd and HighAdd MCLs respectively, indicating a high degree of correspondence between real and simulated MCLs, not only in terms of VA magnitudes, but also in the relative performance throughout the focus. Only two subjects (S3 and S6) showed rho values <0.5, with HighAdd MCLs.     Figure 6 shows TFVA curves averaged across subjects for all additions (LowAdd, orange; MediumAdd, green; HighAdd, purple; NoLens, grey). Solid lines correspond to real MCLs on eye while the dashed lines correspond to simulated MCLs. The average RMS difference between real and SLM simulated MCLs in the TFVA curves was 0.016 ± 0.004, 0.013 ± 0.004, 0.025 ± 0.009 for Low, Medium and High additions, respectively. Figure 7 shows the Bland-Altman plot of averaged VA data across subjects for different MCL conditions. For the Low and MediumAdd the confidence intervals were ±0.01 logMAR, i.e., with differences in VA less than 1 letter (considering each letter has a value of 0.02log units), while for HighAdd the confidence interval was ±0.06 logMAR (difference of 3 letters). The average bias was -0.049, -0.039 and -0.035 logMAR for LowAdd, MediumAdd and HighAdd respectively. In addition, a highly significant shape similarity was found between the real MCLs on eye and the simulated MCLs for all additions (Crossed correlation: LowAdd: k=0. rho=0.995; MediumAdd: k=0, rho=0.994; HighAdd: k=0, rho=0.832, averaged across all subjects).

Discussion
MCLs are increasingly becoming a strategy for management of presbyopia and have also proven to be a therapeutic option for reducing or stop myopia progression. Visual simulation is a suitable technique to easily test the impact of MCL design on vision, allowing rapid comparison across MCL design parameters on the same patient, isolating aspects solely related to design, as opposed to MCL fitting or wearability. Several reports in the literature present the use of AO visual simulators to simulate visual performance with multifocal designs, both testing experimental lens designs or commercial intraocular lenses [19,22,29]. In an earlier study we investigated the representation of MCLs in a simultaneous vision simulator (SimVis), working under the principle of temporal multiplexing. In this study, we compared vision through real MCLs on eye and simulation of the MCLs in a SLM of a laboratory AO device in the same subjects. Validation of the spatial phase representation of a MCL (calculated from the MCL power map) against performance with the real MCL is essential, as this is a common assumption in all simulators, and an intermediate step in SimVis simulations.
In this study, center-near MCLs of three different additions (low, medium and high) were investigated. Potential differences in MCL performance associated to lens base power (i.e., lens thickness and central-near zone diameter) were eliminated by having all patients wear -2 D for far distance. Also, measurements were performed under cycloplegia to eliminate potential effects of accommodation and under a fixed pupil diameter. The effect of the tested MCLs to expand depth-of-focus with increasing near addition was observed with both the real MCLs and the SLM-simulation of the MCLs (TFVA curves, Figs. 3 and 6), and for the SLM-simulated MCL on bench (1-P correlation metric in Fig. 2). These results compare well with previous literature. The Average VA values found in this study are close to those found in previous studies that used the same MCLs, paralyzed accommodation and similar pupil diameters (4-5 mm). A previous report using SimVis simulated lenses [21] reported VA of 0.31 logMAR at Near, 0.13 logMAR at Intermediate and -0.06 logMAR at Far. A study measuring performance of the real MCLs [11] on eye reported VA of 0.37 logMAR at Near, 0.12 logMAR at Intermediate and -0.05 logMAR at Far. Those values are within the range of our report with SLM-simulated and real MCLs reported here: 0.27 vs 0.37 logMAR at Near, 0.09 vs 0.12 logMAR at Intermediate and -0.06 vs -0.05 logMAR at Far, for SLM vs real MCL at 40 cm & 67 cm for Near and Intermediate distances. VA at intermediate and near are generally better under free accommodation (subjects with low and medium additions typically have some residual accommodation). As in previous studies, differences in performance with the same MCL across subjects must arise from different ocular aberration patterns across subjects (and their interactions with the lens optics) as well as neural factors.
A comparison of the TFVA with SLM simulated MCLs and with the real MCLs shows that, on average, the discrepancies are within -0.04 logMAR. In general, the shape similarity metric between simulated and real MCLs (representing the relative TF performance) is high. Interestingly, although the average TF differences are below statistical significance, there is a slight bias towards a better performance (17% to 22.2%) with the SLM simulation than with the real MCL. Individually, there are subjects/conditions where there was almost a perfect match between simulation and real MCL (i.e., S1, all MCLs; S3 MediumAdd lenses; S5, all MCLs) as seen in Fig. 3. The high degree of similarity between the simulated and the real lens was found at various defocus values in each subject and addition power, respectively. In some other cases, the simulated MCL overperforms the real MCL at almost all distances (S4). However, most notably, differences above 0.1 logMAR occur only in some isolated defocus conditions, primarily with HighAdd MCLs. We speculate that these discrepancies may also arise from MCLs decentrations or tear film disruption, effects related to movement during blinking that are present with real MCLs on eye but not with thesimulations in the SLM and other reasons could also be the contribution of the tear lenses. Given that discrepancies tend to be larger with HighAdd MCL, the effect of MCL decentrations appears to be the most plausible explanation.
Our study reveals that the SLM simulator can reliably be used for rotationally symmetric center-near MCLs to provide subjects with the experience of multifocal vision, replicating the visual experience at far, intermediate and near distances provided by real MCLs. This study was performed in an experimental setting, with the SLM implemented in an AO system, a fixed pupil diameter, and monochromatic stimuli. While the SLM has been shown to appropriately represent the phase maps describing the MCL optics, various drawbacks remain: (1) potential chromatic artifacts, as the phase map is accurately mapped on the SLM for a single wavelength. These artifacts were not present in the current study as we matched the illuminating wavelength to the phase map calculations, but may be an issue with polychromatic targets [41]; (2) reflective nature of the SLM, limiting the ability to produce a very compact simulator; (3) small field of view (2 deg), not a problem in visual acuity testing, but limits the ability to represent real world scenes. SimVis simulators based on the principle of temporal multiplexing are not limited by these drawbacks. However, they critically rely on the MCLs being well represented by a phase map (used to calculate the MCL thru-focus performance, which is the target of the SimVis temporal pattern, for each MCL).
The current study demonstrates that the implicit assumptions in the phase map representation of the MCL are, for the most part, valid. In a previous study [21] we compared TFVA with real MCLs and MCL simulations in SimVis. Unlike the current study, MCLs of various base powers (ranging from -9D to +6D) were tested, and each patient was only fitted with one MCL design (the one recommended by the fitting guide protocol). Nevertheless, the degree of through focus performance similarity with the SimVis MCL and the real MCL was comparable to that found in the current study in which MCLs were simulated using SLM, with a similar shape similarity metric (k=0 & rho = 0.895, rho = 0.944, and rho = 0.915, for the Low, Medium, and HighAdd respectively). In the earlier study using SimVis it was found that on average the real MCLs outperformed VA measurements with the SimVis simulations. The slightly better VA (16.6% on average) with real than SimVis simulated MCLs could result from some lack of compensation of the eye's optics (i.e., positive spherical aberration of the eye and negative spherical aberration in the MCL) which may occur with real MCLs but is not possible under temporal multiplexing. Furthermore, current improvements in the corrections of dynamic effects in optotunable lenses [31,32] have led to more accurate representations of the TF optical performance by SimVis, and could ultimately result in an even better match between the SimVis-simulated MCLs and real MCLs in line with the findings of the current study. The current and referred earlier study used high contrast visual acuity targets to assess visual performance. However, other metrics can be more representative of visual quality in the real life. In a recent study [42], we presented a multifocal acceptance score metric MAS-2EV where natural images representing day and night time scenes at far and near were presented, which provides a more comprehensive evaluation of vision in the real world. At the same time, it is well suited to evaluate vision with multifocal corrections (simulated or real) in a clinical environment, as it can be administered in around 2 minutes per correction, particularly with the SimVis simulator.
In summary, our study reveals that the SLM can be used reliably to provide subjects with the experience of multifocal vision before physically trying them on the eye, replicating the visual quality at various distances provided by the real center-near MCLs under test. Measurements were conducted with fixed pupil diameters and paralyzed accommodation. As the goal of the study was to compare the visual performance of the real MCLs on eye and the SLM-simulated MCLs, we did not attempt to fully characterized performance in more natural conditions. Besides, the comparison was limited to high contrast visual acuity and did not attempt to capture other perceived visual quality aspects, as possible with other psychophysical paradigms using natural images [30,31,42,43]. However, the subjects informally reported high correspondence in the perceived quality of the E letters between real MCLs and simulation, except in conditions where tear film break up or decentration disrupted quality with the real MCL. In conclusion, spatial phase map representations of MCLs, mapped in a SLM, are able to represent the profile design of the MCLs (at least in monochromatic light), isolating MCL design aspects from those associated to lens wearability and physiology. Accurate visual simulations of MCLs holds high promise in the contactology practice and even prior to new lens manufacturing, allowing patients to experience different MCL designs rapidly and in a fully non-invasively manner. In future studies we will consider simulating center distance MCLs as those lenses are used in both presbyopia correction, and more frequently for controlling myopia progression.