Understanding In Vivo Chromatic Aberrations in Pseudophakic Eyes Using on Bench and Computational Approaches
Understanding In Vivo Chromatic Aberrations in Pseudophakic Eyes Using on Bench and Computational...
Vinas-Pena, Maria;de Castro, Alberto;Dorronsoro, Carlos;Gonzalez-Ramos, Ana;Redzovic, Suad;Willet, Nicolas;Garzon, Nuria;Marcos, Susana
2022-03-30 00:00:00
hv photonics Article Understanding In Vivo Chromatic Aberrations in Pseudophakic Eyes Using on Bench and Computational Approaches 1 , 2 , 1 1 , 3 1 4 Maria Vinas-Pena *, Alberto de Castro , Carlos Dorronsoro , Ana Gonzalez-Ramos , Suad Redzovic , 4 5 , 6 1 , 7 Nicolas Willet , Nuria Garzon and Susana Marcos Institute of Optics, Spanish National Research Council (CSIC), 28006 Madrid, Spain; a.decastro@csic.es (A.d.C.); cdorronsoro@2eyesvision.com (C.D.); am.gonzalez@csic.es (A.G.-R.); smarcos2@ur.rochester.edu (S.M.) Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02139, USA 2EyesVision, 28760 Madrid, Spain BVI Medical, 4031 Liege, Belgium; sredzovic@bvimedical.com (S.R.); nwillet@bvimedical.com (N.W.) Department Optometry and Vision, Complutense University Madrid (UCM), 28037 Madrid, Spain; nugarzon@opt.ucm.es Miranza IOA Madrid, 28003 Madrid, Spain Center for Visual Science, Department of Ophthalmology, The Institute of Optics, University of Rochester, New York, NY 14642, USA * Correspondence: mvinaspena@mgh.harvard.edu Abstract: Diffractive multifocal intraocular lenses (IOLs) modulate chromatic aberration and re- duce it at certain distances due to interactions between the refractive and diffractive chromatic components. However, the extent to which computer modeling and on bench measurements of IOL chromatic aberration translate to chromatic aberration in patients implanted with these multifocal IOLs (MIOLs) is not yet fully understood. In this study, we compare the chromatic difference of focus and longitudinal chromatic aberrations in pseudophakic patients implanted with different IOL Citation: Vinas-Pena, M.; de Castro, designs (monofocal and trifocal IOLs) and materials (hydrophobic and hydrophilic), and compared A.; Dorronsoro, C.; Gonzalez-Ramos, them with predictions from computer eye models and on bench measurements with the same IOLs. A.; Redzovic, S.; Willet, N.; Garzon, Patient data consisted of results from 63 pseudophakic eyes reported in four different studies and N.; Marcos, S. Understanding In Vivo obtained psychophysically in the visual testing channel of a custom-developed polychromatic adap- Chromatic Aberrations in tive optics system. Computational predictions were obtained using ray tracing on computer eye Pseudophakic Eyes Using on Bench models, and modulation transfer function (MTF) on bench measurements on physical eye models. and Computational Approaches. We found that LCA (in vivo/simulated) for far vision was 1.37 0.08 D/1.19 D for monofocal Photonics 2022, 9, 226. https:// doi.org/10.3390/photonics9040226 hydrophobic, 1.21 0.08 D/0.88 D for monofocal hydrophilic, 0.99 0.06 D/1.19 D for MIOL hy- drophobic, and 0.82 0.05 D/0.88 D for MIOL hydrophilic. For intermediate and near vision, LCA Received: 16 February 2022 (in vivo/simulated) was 0.67 0.10 D/0.75 D and 0.23 0.08 D/0.19 D for MIOL hydrophobic and Accepted: 26 March 2022 0.27 0.15 D/0.38 D and 0.15 0.15 D/ 0.13 D for MIOL hydrophilic, respectively. In conclusion, Published: 30 March 2022 computational ray tracing and on bench measurements allowed for evaluating in vivo chromatic Publisher’s Note: MDPI stays neutral aberration with different materials and designs for multifocal diffractive intraocular lenses. with regard to jurisdictional claims in published maps and institutional affil- Keywords: chromatic aberration; polychromatic optical quality; pseudophakic eye; intraocular lenses; iations. multifocal designs; visual simulation; diffractive designs Copyright: © 2022 by the authors. 1. Introduction Licensee MDPI, Basel, Switzerland. This article is an open access article Diffractive multifocal intraocular lenses (MIOLs) allow for modulating chromatic aber- distributed under the terms and ration to expand the range of vision in multifocal optical designs [1], therefore improving conditions of the Creative Commons vision in pseudophakic eyes. However, the balance of the eye’s natural aberrations and IOL Attribution (CC BY) license (https:// design, and their combined impact on vision are not yet fully understood. In particular, creativecommons.org/licenses/by/ the polychromatic retinal image and visual quality are affected by interactions between 4.0/). Photonics 2022, 9, 226. https://doi.org/10.3390/photonics9040226 https://www.mdpi.com/journal/photonics Photonics 2022, 9, 226 2 of 16 monochromatic and chromatic aberrations, which are altered when the crystalline lens of the eye is replaced by an intraocular lens (IOL). Chromatic effects in the eye arise from the wavelength-dependence of the refractive index of the ocular media [2–4]. In particular, chromatic dispersion causes short wave- lengths to focus in front of long wavelengths, producing a chromatic difference of focus between the shorter and longer wavelengths, known as longitudinal or axial chromatic aberration (LCA) [5]. In addition, misalignments between the ocular components, the off-axis position of the fovea, and optical irregularities, result in a transversal shift of focus for different wavelengths, known as transverse chromatic aberration (TCA) [6–10]. Polychromatic optical quality on the phakic eye depends on the delicate balance between monochromatic and chromatic aberrations (LCA and TCA) and their interactions [10–12]. It is fairly accepted that LCA is rather constant across the population [4], around 2D in the visible range using subjective techniques [11] and slightly lower using reflectometric methods [13–15], with low inter subject variability (below 0.10 D with both) [11]. In pseudophakic eyes, where an intraocular lens (IOL) replaces the natural crystalline lens of the eye, the amount of LCA changes [16–19], as well as the balance between ocular aberrations (mono- and chromatic) [20], and the optical performance of pseudophakic eyes implanted with monofocal IOL in polychromatic light will depend on the Abbe number of the IOL material (ranging in most of lenses from 35 to 60; the higher the Abbe num- ber, the lower the LCA) [19,21]. Moreover, various studies report the LCA of lenses with different materials, both on bench and once implanted in the eye [16–18,20,22–25], with differences consistent with the Abbe number of the materials and independent of the IOL power [15]. However, the question remains about the impact on visual performance due to the significantly different phakic-pseudophakic LCA (i.e., with hydrophilic materials [15]). In multifocal diffractive IOLs [26–28], both the material and the design [28–32] determine the through-focus visual performance (either in intraocular [33] or contact lenses [34,35]), with hybrid refractive-diffractive designs that split light energy between a number of foci, aiming at providing multifocality at the expense of reducing optical quality at all distances. In most designs, the far focus receives light that is purely refracted (0 diffraction order), whereas the other focus (intermediate and near) are generated with light refracted by the lens and diffracted by the multifocal add (first and second order of diffraction). Refractive or diffractive focalization leads to opposite signs of LCA, thus allowing modulating the chromatic aberration of the eye at different distances. Using diffractive optics, it is possible to alter [36,37] and even change the sign of the chromatic aberration induced by the lens, at least in several foci [32,38]. All patients implanted with first-generation multifocal IOLs (generally bifocal) reported good vision at far and near [39,40], but experienced a significant reduction in visual acuity at intermediate distances [41]. For this reason, state-of-the-art multifocal IOLs are generally designed to avoid the gaps of bifocal designs [42]. For this purpose, shifts in the position of the foci peaks of diffractive bifocal lenses with wavelengths have also been used as a strategy to “fill in” those intermediate distances, with lower energy contributions, and mimic an extended depth-of-focus in polychromatic light. Evaluations of the optical through-focus performance of these MIOLs [43,44] are gen- erally performed on bench, by measuring through-focus image quality and modulation transfer function (MTF) [37,45], from the light distribution and efficiency of the different foci [46], for different visible wavelengths. This approach allows for evaluating the LCA and through-focus energy efficiency of different designs and materials of bifocal IOLs [47], where for far-vision, the chromatic defocus due to the refractive base power was additive to the LCA of the ocular media, while in near-vision, the achromatizing effect of diffractive bifocal-IOLs compensated, in part, the natural eye’s LCA. Loicq et al. characterized on bench [38] the through-focus MTF of a trifocal diffractive IOL in red, green, and blue wavelengths (480 nm, 546 nm, and 650 nm, respectively), to obtain the chromatic difference of focus and to confirm a compensatory effect between refractive and diffractive contribu- tions for certain foci in diffractive lenses, the actual magnitude depends on material and design. These differences in the through-focus optical performance likely reflect on the Photonics 2022, 9, 226 3 of 16 through-focus visual performance in patients. In two recent studies [48,49], we presented the subjective LCA measured in vivo in eyes implanted with the same design of trifocal diffractive IOL but different materials. In the first study, LCA was measured in 10 subjects (20 eyes) implanted with the hydrophilic trifocal diffractive IOL (FineVision POD F), at three different viewing distances (0D/+1.75D/+3.50 D) in a spectral range of 480–700 nm. We found that subjective-LCA was higher for far (0.82 0.05 D) than for intermediate (0.27 0.15 D) and near (0.15 0.15 D) distances. Similar trends, but higher amounts of LCA, were found in a subsequent study with hydrophobic MIOLs (FineVision HP), where subjective-LCA was 0.99 0.06 D, 0.67 0.10 D, and 0.23 0.08 D for far, intermediate, and near distances, respectively. The dependence of the magnitude of LCA on distance is in agreement with previous studies using optical simulations or on-bench measurements [32], with on-bench-LCA showing higher values than in vivo measurements, particularly for far vision. In general, we found a lower LCA magnitude for the multifocal IOLs at far, with respect to the LCA for the monofocal IOLs [15], with similar shifts in both lenses (hydrophilic 0.39 D difference and hydrophobic 0.38 D difference). A decrease was also found for double-pass results (0.16 D difference) for hydrophilic data. However differences were found with on-bench data [38] on the same MIOLs, which showed higher amounts of LCA than those for in vivo patients, where intermediate and near LCA were reduced or almost fully cancelled, respectively. An interesting approach to address those differences is the use of computational ray tracing models to simulate the polychromatic optical quality in pseudophakic eyes im- planted with an IOL. Computer eye models allowed for improving the selection of the optimal IOL power to be implanted in cataract surgery [50–52]. Moreover, customized eye models constructed using the anatomical parameters of individual patients have been shown to reproduce accurately the higher-order aberrations measured with an aberrome- ter [53,54]. Thus, these models can be used as platforms to test the polychromatic optical performance with a particular IOL design. In this study, we present the chromatic dif- ference of focus and longitudinal chromatic aberration in 5 phakic and 63 pseudophakic eyes implanted with different IOLs designs and materials, obtained from computational ray tracing, on bench and in vivo measurements using a custom-developed polychromatic adaptive optics system across four different studies 2. Materials and Methods Computational ray tracing, on bench calibrations and in vivo measurements, using a custom-developed polychromatic AO system, were performed in 63 eyes implanted with different IOLs designs and materials to assess multifocal pseudophakic vision. 2.1. Intraocular Lenses Four IOLs of different designs and materials (monofocal, multifocal, hydrophobic, and hydrophilic) were evaluated in the study. Monofocal lenses were the PhysIOL PodEye dou- ble C Loop hydrophobic lens and the PhysIOL PodAY hydrophilic lens, both monofocal and aspheric. Multifocal lenses were aspheric trifocal diffractive IOLs, built with a combination of two bifocal diffractive patterns, of which one was for far and near-vision and the other for far and intermediate-vision. IOLs have a diffractive anterior surface entirely convoluted. By varying the step height of the diffractive structure of the IOL across the pupil, the energy distribution for different distances can be controlled. Indeed, the amount of energy directed to far-vision focus is superior to that directed to intermediate- and near-vision foci with increasing apertures, by means of a gradual decrease in the height of diffractive steps from the center to the periphery, which is also the case for the refractive multifocal IOL [37]. The apodized design of the lens benefits the far focus against near/intermediate focus for larger pupils. The energy balance was, as expected, wavelength-dependent, due to variations of diffraction efficiency with wavelength. The combination of the two diffractive structures provided three useful focal distances: 0.0 D for far-vision, +1.75 D addition for intermediate- vision, and +3.50 D addition for near-vision [55]. The implanted lenses were hydrophilic Photonics 2022, 9, x FOR PEER REVIEW 4 of 17 against near/intermediate focus for larger pupils. The energy balance was, as expected, wavelength-dependent, due to variations of diffraction efficiency with wavelength. The Photonics 2022, 9, 226 4 of 16 combination of the two diffractive structures provided three useful focal distances: 0.0 D for far-vision, +1.75 D addition for intermediate-vision, and +3.50 D addition for near-vi- sion [55]. The implanted lenses were hydrophilic FineVision POD F and hydrophobic FineVision POD F and hydrophobic FineVision HP (POD F GF), manufactured by PhysIOL FineVision HP (POD F GF), manufactured by PhysIOL (Liege, Belgium). Figure 1 summa- rizes the materi (Liege, al and des Belgium). igns char Figur acter eis 1tics summarizes for all IOLs ( the a), material as well as dep and designs icts the m charact ono- eristics for all chromatic theoIOLs retica (a) l thro , asu well gh-foc as u depicts s performance the monochr of the IOL omatic altheor one in etical green thr ligh ough-focus t (546 nm) performance , of the IOL alone in green light (546 nm), in terms of Visual Strehl for all four IOLs (b). in terms of Visual Strehl for all four IOLs (b). Figure 1. Intraocular lenses. (a) Material and designs characteristics for all IOLs; (b) monochromatic Figure 1. Intraocular lenses. (a) Material and designs characteristics for all IOLs; (b) monochro- optical quality metric (546 nm) in the form of Visual Strehl (4 mm) for all four IOLs: mono-hydro- matic optical quality metric (546 nm) in the form of Visual Strehl (4 mm) for all four IOLs: mono- phobic (solid light green); MIOL-hydrophobic (dashed light green); Mono-hydrophilic (solid dark hydrophobic (solid light green); MIOL-hydrophobic (dashed light green); Mono-hydrophilic (solid green); MIOL-hydrophilic (dashed dark green). dark green); MIOL-hydrophilic (dashed dark green). 2.2. Computational Simulations 2.2. Computational Simulations Pseudophakic computer eye models were implemented in OpticStudio (Zemax, Pseudophakic computer eye models were implemented in OpticStudio (Zemax, Kirk- Kirkland, WA, USA) and computational ray tracing was used to study the through-focus land, WA, USA) and computational ray tracing was used to study the through-focus optical quality as a function of the wavelength. The chromatic difference of focus and the optical quality as a function of the wavelength. The chromatic difference of focus and longitudinal chromatic aberration were calculated with different intraocular lenses. Fig- the longitudinal chromatic aberration were calculated with different intraocular lenses. ure 2 illustrates the computational ray tracing methodology, where a pseudophakic phys- Figure 2 illustrates the computational ray tracing methodology, where a pseudophakic iological eye model was used (Figure 2a) to simulate the IOL-on-eye. The model was based physiological eye model was used (Figure 2a) to simulate the IOL-on-eye. The model was on the Liou and Brennan eye model [56], where the crystalline lens was replaced by the based on the Liou and Brennan eye model [56], where the crystalline lens was replaced by intraocular lens under the intraocular study and the lens under anterior cham study and be the r dep anterior th was set chamber to 4.5 m depth m. Th was e wav seteto - 4.5 mm. The length-dependent r wavelength-dependent efractive index of th refractive e corne index a, aqueous, an of the cornea, d vitreous were o aqueous, and vitr btained eous were obtained from the four-term Cauchy equations derived by Atchison and Smith [4]. The LCA of from the four-term Cauchy equations derived by Atchison and Smith [4]. The LCA of pseudophakic eye models was calculated in computational model eyes from the power pseudophakic eye models was calculated in computational model eyes from the power differences between the peaks in the through-focus curves for different wavelengths (480, differences between the peaks in the through-focus curves for different wavelengths (480, 546, and 700 nm). 546, and 700 nm). The through-focus optical quality was studied with monofocal and multifocal IOL The through-focus optical quality was studied with monofocal and multifocal IOL designs of hydrophobic and hydrophilic materials. MIOLs were simulated adding a flat designs of hydrophobic and hydrophilic materials. MIOLs were simulated adding a flat thin phase surface representing the diffractive multifocal component to a monofocal IOL of thin phase surface representing the diffractive multifocal component to a monofocal IOL equivalent far power. The ray tracing software was used to calculate the wave aberration of equivalent far power. The ray tracing software was used to calculate the wave aberra- with the base surface and the impacts of the rays on the IOL anterior surface for different tion with the base surface and the impacts of the rays on the IOL anterior surface for dif- pupil positions. A phase was added at those locations to simulate the multifocal add. The ferent pupil positions. A phase was added at those locations to simulate the multifocal phase at each point was calculated as the difference between the multifocal surface and the add. The phase at each point was calculated as the difference between the multifocal sur- base surface multiplied by the difference in refractive indices. face and the base surface multiplied by the difference in refractive indices. Retinal image quality metrics were computed for each wavelength (480–700 nm) Retinal image quality metrics were computed for each wavelength (480–700 nm) and and distance (far, intermediate, and near vision) (Figure 2b). The Point Spread Function distance (far, intermediate, and near vision) (Figure 2b). The Point Spread Function and and Modulation Transfer Function were calculated using standard Fourier Optics- based Modulation Transfer Function were calculated using standard Fourier Optics- based rou- routines written in MATLAB (MathWorks, Natik, MA, USA), in a 6D focus range, in 0.1-D tines written in MATLAB (MathWorks, Natik, MA, USA), in a 6D focus range, in 0.1-D steps for a 4-mm pupil diameter. Retinal image quality was described in terms of the Visual Strehl ratio (VS), calculated from the wave aberration (4 mm pupil size) as the relative volume under the MTF (normalized to that of diffraction limit system) weighting the frequency components with an average neural contrast sensitivity function [57,58]. Photonics 2022, 9, x FOR PEER REVIEW 5 of 17 steps for a 4-mm pupil diameter. Retinal image quality was described in terms of the Vis- ual Strehl ratio (VS), calculated from the wave aberration (4 mm pupil size) as the relative Photonics 2022, 9, 226 5 of 16 volume under the MTF (normalized to that of diffraction limit system) weighting the fre- quency components with an average neural contrast sensitivity function [57,58]. Figure 2. Illustration of the computational ray tracing methodology. (a) Representation of the pseu- Figure 2. Illustration of the computational ray tracing methodology. (a) Representation of the pseu- dophakic physiological eye model in Zemax to simulate implanted IOL eye conditions. (b) Optical dophakic physiological eye model in Zemax to simulate implanted IOL eye conditions. (b) Optical quality metric flow chart. LCA and chromatic difference of focus were obtained from the TFVS quality metric flow chart. LCA and chromatic difference of focus were obtained from the TFVS curves curves for the different wavelengths (480–700 nm). for the different wavelengths (480–700 nm). 2.3. On-Bench Measurements 2.3. On-Bench Measurements Through-focus optical quality for the four IOLs was obtained on bench in terms of Through-focus optical quality for the four IOLs was obtained on bench in terms of the MTF (50 LP/mm) through-focus curves for three different wavelengths (blue: 480 nm; the MTF (50 LP/mm) through-focus curves for three different wavelengths (blue: 480 nm; 546 nm; red: 650 nm), following the procedures described in Loicq et al. (2019) [38]. The 546 nm; red: 650 nm), following the procedures described in Loicq et al. (2019) [38]. The optical bench used for this series of measurements was the PMTF (Power and Modulation optical bench used for this series of measurements was the PMTF (Power and Modulation Transfer Function bench, Lambda-X), which allowed for measurements of image qual- Transfer Function bench, Lambda-X), which allowed for measurements of image quality ity MTF in three different monochromatic wavelengths (480 nm, 546 nm, and 650 nm). MTF in three different monochromatic wavelengths (480 nm, 546 nm, and 650 nm). Meas- Measurements were performed with a model cornea, displaying zero spherical aberration urements were performed with a model cornea, displaying zero spherical aberration (0 (0 mm of longitudinal spherical aberration), to assess the optical performance of the IOLs mm of longitudinal spherical aberration), to assess the optical performance of the IOLs themselves, excluding the potential influence of the cornea lens. themselves, excluding the potential influence of the cornea lens. In the experimental setup, the tested multifocal IOL was placed in an 11.0 mm diameter In the experimental setup, the tested multifocal IOL was placed in an 11.0 mm diam- lens holder before being inserted into a quartz cell filled with 0.9% aqueous sodium chloride. eter lens holder before being inserted into a quartz cell filled with 0.9% aqueous sodium The anterior side of the IOL was placed facing the incident light. The lens holder guaranteed chloride. The anterior side of the IOL was placed facing the incident light. The lens holder a tilt-free orientation of the IOL under inspection. The through-focus MTF curves were guaranteed a tilt-free orientation of the IOL under inspection. The through-focus MTF recorded at 50 LP/mm at a 3.0 mm aperture in three wavelengths for IOLs +20.0 D. Residual curves were recorded at 50 LP/mm at a 3.0 mm aperture in three wavelengths for IOLs chromatic aberration generated by the optical bench was removed by subtracting the LCA +20.0 D. Residual chromatic aberration generated by the optical bench was removed by contribution of the setup without any IOL (optical bench + liquid cell + NaCl solution). subtracting the LCA contribution of the setup without any IOL (optical bench + liquid cell + NaCl solution). 2.4. In Vivo Measurements Chromatic difference of focus (CDF) and longitudinal chromatic aberration were ob- 2.4. In Vivo Measurements tained from prior subjective measurements at different wavelengths and viewing distances Chromatic difference of focus (CDF) and longitudinal chromatic aberration were ob- in phakic and pseudophakic patients implanted with different IOLs designs and materials tained from prior subjective measurements at different wavelengths and viewing dis- reported in four different studies previously published studies by our group. [11,15,48,49]. tances in phakic and pseudophakic patients implanted with different IOLs designs and The collective data used as a reference in the current study consisted of 63 eyes, 58 im- materials reported in four different studies previously published studies by our group. planted with IOLs of different designs and materials (monofocal, multifocal, hydrophobic, [11,15,48,49]. and hydrophilic) and five phakic eyes, all of which are summarized in Table 1. All patients The collective data used as a reference in the current study consisted of 63 eyes, 58 underwent surgery at Miranza IOA (Madrid, Spain). The IOL power of the implanted IOLs implanted with IOLs of different designs and materials (monofocal, multifocal, hydro- ranged between 16.00 and 26.00 D. Data on the patient inclusion criteria, surgical procedure, phobic, and hydrophilic) and five phakic eyes, all of which are summarized in Table 1. All visual outcomes, and approved protocols can be found in the corresponding studies. Photonics 2022, 9, 226 6 of 16 Table 1. Refractive and IOL profile of the patients participating in the different studies. A Phakic eyes Sample 5 young subjects (5 eyes) Age 28.60 1.89 years Subjective refraction 0 to 4.50 D ( 1.15 0.95 D); astigmatism 0.5 D Measurements Monocular Crystalline lens Vinas et al. BOE 2015 Study doi: 10.1364/OE.23.00948 B Pseudophakic eyes B.1 Patients implanted with hydrophilic and hydrophobic monofocal IOL Sample 9 subjects (18 eyes) Age 73.92 4.28 years 3.25 to +3.00 D (Sph: +0.18 0.26 D; Subjective refraction cyl: 0.42 0.52 D) Monofocal hydrophilic and Measurements Monocular. Both eyes (Bilateral implantation) hydrophobic IOL IOL design Monofocal asferic Hydrophilic (Abbe number: 58; RI: 1.46; PODAY) IOL material Hydrophobic (Abbe number: 41.91; RI: 1.52; PODEYE) Vinas et al. JCRS 2015 Study doi: 10.1016/j.jcrs.2015.11.009 B.2 Patients implanted with hydrophilic M-IOL Sample 10 subjects (20 eyes) Age 66.70 3.25 years 0.75 to + 0.75 D (Sph: +0.06 0.170 D; Subjective refraction cyl: 0.28 0.40 D) Trifocal hydrophilic Measurements Monocular. Both eyes (Bilateral implantation) MIOL IOL design Trifocal diffractive IOL material Hydrophilic (Abbe number: 58; RI: 1.46; POD F) Vinas et al. JRS 2017 Study doi: 10.3928/1081597X-20170814-01 B.3 Patients implanted with hydrophobic M-IOL Sample 10 subjects (20 eyes) Age 64.56 3.52 years 1.00 to + 1.25 D (Sph: 0.05 0.13 D; Subjective refraction cyl: 0.19 0.34 D) Trifocal hydrophobic Measurements Monocular. Both eyes (Bilateral implantation) MIOL IOL design Trifocal diffractive IOL material Hydrophobic (Abbe number: 41.91; RI: 1.52; POD F GF) Vinas et al. JRS 2020 Study doi: 10.3928/1081597X-20200930-01 RI: refractive index; MIOL: multifocal intraocular lens; LCA measurements were obtained using a custom-developed 8-channels polychro- matic Adaptive Optics (AO) system at the Visual Optics and Biophotonics Laboratory (Instituto de Optica, Consejo Superior de Investigaciones Científicas), described in detail in previous publications [11,12,33,34,59]. For the purposes of the current comparison, we used data from psychophysical best focus measurements at five different wavelengths in visible light (480, 532, 555, 650, and 700 nm) at far (phakic and monofocal IOLs), and additionally at intermediate (+1.75 D) and near (+3.5 D) distances. Subjects selected the best subjective focus using a remote control to move a Badal Optometer while viewing a Maltese cross as a fixation target (1.62 deg angular subtend) displayed on a Digital Micromirror Device (DLP Discovery™ 4100 0.7 XGA, Texas Instruments, Dallas, TX, USA), placed in a conjugate retinal plane, and illuminated with the monochromatic light from a supercontinuum laser in combination with a dual acousto-optic tunable filter. All reported measurements were performed under mydriasis (Tropicamide 1%; 2 drops 30 min prior to the beginning of the Photonics 2022, 9, 226 7 of 16 study, and 1 drop every 1 h), using fixed pupil diameters (6-mm pupils in phakic eyes and 4-mm pupils in pseudophakic eyes) 2.5. Data Analysis Computer simulations. The chromatic difference of focus (CDF) was obtained from the focus positions of the peaks in the computed TFVS curves at different wavelengths and distances. The LCA was estimated as the chromatic difference of focus between 480 and 700 nm. On-bench measurements. The CDF and LCA were obtained from the positions of the peaks of the MTF through-focus curves (50 LP/mm) at different wavelengths and distances. The LCA was estimated as the chromatic difference of focus between 480 and 650 nm. In vivo measurements. Chromatic difference of focus (CDF) curves were obtained from the selected best foci (readings of the Badal optometer) at each wavelength (480–700 nm). The LCA was obtained from linear fittings to the CDF curves, as the difference of focus between 480 and 700 nm. In all cases, the curves were shifted in the vertical axis so that they crossed zero at 550 nm (the reference wavelength) for a unique reference. Statistical analysis was performed with SPSS software (International Business Machines Corp.) to test differences in the estimated longitudinal chromatic aberration across experiments and conditions. A paired-samples t-test was performed to analyze specific differences between conditions. Standard deviation was used to test intersubject variability in the in vivo experiments. 3. Results Computational ray tracing, on bench calibrations and in vivo measurements, using a custom-developed polychromatic adaptive optics system, in 63 eyes implanted with different IOLs designs and materials were used to assess multifocal pseudophakic vision. 3.1. Computational Ray Tracing: Polychromatic Phakic and Pseudophakic Optical Quality Optical quality metrics were obtained using computational ray tracing for the phakic model eyes in combination with both materials and IOL designs, for blue (480 nm), green (546 nm), and red (700 nm), in the form of TF Visual Strehl curves (Figure 3a). Chromatic difference of focus was obtained from the focus positions of the peaks of the TFVS curves for the different wavelengths and distances, as shown in Figure 3b. Slopes of the CDF curves were very similar for the monofocal implanted eyes for far vision, independently of the material of the lens (Table 2), where slopes differed significantly for near vision. In intermediate vision, slopes were similar, but CDF curves differed in the red light region. LCA (480–700 nm), obtained from the focus positions of the peaks of the TFVS curves for the different wavelengths and distances, was higher for hydrophobic than for hydrophilic material for both monofocal and multifocal IOLs for far vision (mono- hydrophobic: 1.19 D; mono-hydrophilic: 0.88 D; MIOL-hydrophobic: 1.19 D; MIOL- hydrophilic: 0.88 D), but lower than that of the phakic eye (1.13 D). A similar trend, higher LCA for hydrophobic material, was also found at intermediate and near distances (MIOL-hydrophobic: Intermediate 0.75 D and Near 0.19 D; MIOL-hydrophilic: Int 0.38 D and Near 0.13 D). These differences in the LCA of the hydrophobic and the hydrophilic lenses were determined by the different Abbe numbers of the material (LCA hydrophobic Abbe 41.91 > LCA hydrophilic Abbe 58, for far vision). Photonics 2022, 9, x FOR PEER REVIEW 8 of 17 Photonics 2022, 9, 226 8 of 16 by the different Abbe numbers of the material (LCA hydrophobic Abbe 41.91 > LCA hy- drophilic Abbe 58, for far vision). Figure 3. Computational ray tracing. (a) Visual quality metric in the form of Visual Strehl for pseu- Figure 3. Computational ray tracing. (a) Visual quality metric in the form of Visual Strehl for dophakic model eyes (4 mm) in combination with both materials (empty circles with dotted lines pseudophakic model eyes (4 mm) in combination with both materials (empty circles with dotted lines hydrophobic and filled circles with continuous lines hydrophilic) and designs IOLs for blue (480 hydrophobic and filled circles with continuous lines hydrophilic) and designs IOLs for blue (480 nm), nm), green (546 nm), and red (700 nm), and (b) chromatic difference of focus (CDF) for all condi- green (546 nm), and red (700 nm), and (b) chromatic difference of focus (CDF) for all conditions. tions. 3.2. On-Bench Measurements 3.2. On-Bench Measurements Figure 4 summarizes the on-bench measurements in terms of MTF (50 LP/mm) Figure 4 summarizes the on-bench measurements in terms of MTF (50 LP/mm) for for monofocal, multifocal, hydrophobic, and hydrophilic IOLs, for blue (480 nm), green monofocal, multifocal, hydrophobic, and hydrophilic IOLs, for blue (480 nm), green (546 (546 nm), and red (650 nm) (a–c), as well as the chromatic difference of focus (CDF) for the nm), and red (650 nm) (a–c), as well as the chromatic difference of focus (CDF) for the monofocal and multifocal IOLs for far (gray lines), intermediate (yellow lines), and near monofocal and multifocal IOLs for far (gray lines), intermediate (yellow lines), and near (purple lines) distances (d–e). Finally, the longitudinal chromatic aberration (LCA) for the (purple lines) distances (d–e). Finally, the longitudinal chromatic aberration (LCA) for the 480–650 spectral range for far (gray), intermediate (yellow), and near (purple) distances is 480–650 spectral range for far (gray), intermediate (yellow), and near (purple) distances is shown. In the monofocal IOLs, LCA was higher for the hydrophobic material (0.59 D and shown. In the monofocal IOLs, LCA was higher for the hydrophobic material (0.59 D and 0.31D for the hydrophobic and the hydrophilic, respectively). 0.31D for the hydrophobic and the hydrophilic, respectively). For both MIOLs, material and design determined the LCA of the lens at each visual For both MIOLs, material and design determined the LCA of the lens at each visual distance. For far vision, where only the refractive component of the lens was present, LCA distance. For far vision, where only the refractive component of the lens was present, LCA was 0.73 D and 0.39 D for the hydrophobic and the hydrophilic lens, respectively, higher was 0.73 D and 0.39 than in D f the or monofocal the hydrophobi IOL case. c and In the h the case ydrophilic of nearle vision, ns, respective where rly, high efractive er and diffractive than in the monofocal IOL case. In the case of near vision, where refractive and diffractive components were at play, LCA was 0.55 D and 0.87 D, respectively. Both refractive components were at play, and diffractive LCA was components −0.55 D an have d opposite −0.87 D, resp signs. ectiv Ineparticular ly. Both re , fr red activ light e and focused first due diffractive components h to the diffractive ave opposite signs. component ( In par LCA), ticular, r while blue ed lig light ht foc focused used fir first st d due ue to to the refractive the diffractive component component ((+LCA). −LCA), wh This ile blue resulted lighin t fo acused negative first LCA, due to th higher e refrac for hydr tive com ophilic - than for hy- drophobic, as a consequence of the lower material dispersion of the hydrophilic multifocal ponent (+LCA). This resulted in a negative LCA, higher for hydrophilic than for hydro- phobic, as a co lens. nsequence o For intermediate f the lower m vision, aterial behavior dispersion of differedthe h between ydrophilic m the twou materials. ltifocal In the case of hydrophobic lens, LCA was 0.35 D, while for the hydrophilic was 0.09 D, due to the lens. For intermediate vision, behavior differed between the two materials. In the case of different interactions between the refractive and diffractive components. hydrophobic lens, LCA was 0.35 D, while for the hydrophilic was −0.09 D, due to the dif- ferent interactions between the refractive and diffractive components. Photonics 2022, 9, x FOR PEER REVIEW 9 of 17 Photonics 2022, 9, 226 9 of 16 Figure 4. On-bench LCA. (a–c) TF MTF (50 LP/mm) for the monofocal, multifocal, hydrophobic Figure 4. On-bench LCA. (a–c) TF MTF (50 LP/mm) for the monofocal, multifocal, hydrophobic (dashed lines), and hydrophilic (solid lines) for blue (480 nm), green (546 nm), and red (650 nm); (d– (dashed lines), and hydrophilic (solid lines) for blue (480 nm), green (546 nm), and red (650 nm); e) chromatic difference of focus (CDF) for the monofocal and multifocal IOLs, for far (gray lines), (d,e) chromatic difference of focus (CDF) for the monofocal and multifocal IOLs, for far (gray lines), intermediate (yellow lines) and near (purple lines) distances; (f) longitudinal chromatic aberration intermediate (yellow lines) and near (purple lines) distances; (f) longitudinal chromatic aberration (LCA) for the 480–650 spectral range for far (gray), intermediate (yellow), and near (purple) dis- (LCA) for the 480–650 spectral range for far (gray), intermediate (yellow), and near (purple) distances. tances. 3.3. Chromatic Difference of Focus: Far Vision 3.3. Chromatic Difference of Focus: Far Vision Figure 5 shows the average chromatic difference of focus (480–700 nm) for far vision Figure 5 shows the average chromatic difference of focus (480–700 nm) for far vision for (a) phakic subjects, and for (b) monofocal hydrophobic, (c) monofocal hydrophilic, for (a) phakic subjects, and for (b) monofocal hydrophobic, (c) monofocal hydrophilic, (d) (d) multifocal hydrophobic, and (e) multifocal hydrophilic IOLs, obtained with the dif- multifocal hydrophobic, and (e) multifocal hydrophilic IOLs, obtained with the different ferent methods: subjective (gray circles) and computational (yellow squares) techniques. methods: subjective (gray circles) and computational (yellow squares) techniques. Com- Computational ray tracing predicted the general chromatic trends for all conditions well. putational ray tracing predicted the general chromatic trends for all conditions well. Dis- Discrepancies were found in red light for the phakic eye, and in blue light for the monofocal crepancies were found in red light for the phakic eye, and in blue light for the monofocal hydrophilic. Experimental inter-subject variability was significantly higher with the MIOL- hydrophilic. Experimental inter-subject variability was significantly higher with the hydrophilic (0.37 D) than with the hydrophobic (0.06 D) or the monofocal (0.06 D MIOL-hydrophilic (±0.37 D) than with the hydrophobic (±0.06 D) or the monofocal (±0.06 averaged across materials) IOLs (p < 0.01). D averaged across materials) IOLs (p < 0.01). 3.4. Chromatic Difference of Focus: Multifocal IOLs Figure 6 shows the average chromatic difference of focus (480–700 nm) for multifocal (a) hydrophobic and (b) hydrophilic MIOLs for far (0 D), intermediate (1.75 D), and near (3.50 D) vision, measured subjectively (gray circles), and calculated computationally (yellow squares). Differences across testing distances were obtained directly from the experimental data. General trends for multifocal vision with the two materials MIOLs were well predicted by computational ray tracing. In particular, the slopes of the curves for all distances agreed, except in near vision for MIOL-hydrophilic (p < 0.01), where discrepancies arose from the blue-green region. In the hydrophobic MIOLs, the TFVS maximum peaks for near vision shifted from the experimental best subjective focus (555 nm Intermediate: 1.18 D-Computational vs. 1.42 D-Experimental and Near: 2.44 D-Computational vs. 2.82 D-Experimental). Similar to far vision, experimental inter-subject variability was significantly higher with the MIOL-hydrophilic (p < 0.01) for intermediate (0.36 D vs. 0.10 D) and near (0.41 D vs. 0.09 D) vision. Photonics 2022, 9, x FOR PEER REVIEW 10 of 17 Photonics 2022, 9, 226 10 of 16 Figure 5. Average chromatic difference of focus (CDF) for far vision. CDF for (a) phakic subjects, Figure 5. Average chromatic difference of focus (CDF) for far vision. CDF for phakic subjects, and for and for (b) monofocal hydrophobic (N = 9), (c) monofocal hydrophilic (N = 9), (d) multifocal hydro- monofocal hydrophobic (N = 9), monofocal hydrophilic (N = 9), multifocal hydrophobic (N = 20), phobic (N = 20), and (e) multifocal hydrophilic (N = 20) implanted IOLs, measured with subjective and multifocal hydrophilic (N = 20) implanted IOLs, measured with subjective (gray circles), and Photonics 2022, 9, x FOR PEER REVIEW 11 of 17 (gray circles), and computational (yellow squares) techniques. Error bars stand for inter-subject var- computational (yellow squares) techniques. Error bars stand for inter-subject variability in all cases. iability in all cases. 3.4. Chromatic Difference of Focus: Multifocal IOLs Figure 6 shows the average chromatic difference of focus (480–700 nm) for multifocal (a) hydrophobic and (b) hydrophilic MIOLs for far (0 D), intermediate (1.75 D), and near (3.50 D) vision, measured subjectively (gray circles), and calculated computationally (yel- low squares). Differences across testing distances were obtained directly from the experi- mental data. General trends for multifocal vision with the two materials MIOLs were well predicted by computational ray tracing. In particular, the slopes of the curves for all dis- tances agreed, except in near vision for MIOL-hydrophilic (p < 0.01), where discrepancies arose from the blue-green region. In the hydrophobic MIOLs, the TFVS maximum peaks for near vision shifted from the experimental best subjective focus (555 nm Intermediate: −1.18 D-Computational vs. −1.42 D-Experimental and Near: −2.44 D-Computational vs. −2.82 D-Experimental). Similar to far vision, experimental inter-subject variability was sig- nificantly higher with the MIOL-hydrophilic (p < 0.01) for intermediate (±0.36 D vs. ±0.10 D) and near (±0.41 D vs. ±0.09 D) vision. Figure 6. Average chromatic difference of focus (CDF) for multifocal vision. CDF for hydrophobic Figure 6. Average chromatic difference of focus (CDF) for multifocal vision. CDF for hydrophobic and hydrophilic MIOLs for far (0 D), intermediate (1.75 D), and near (3.50 D) vision measured with and hydrophilic MIOLs for far (0 D), intermediate (1.75 D), and near (3.50 D) vision measured subjective (gray circles) and computational (yellow squares) techniques. Error bars stand for inter- with subjective (gray circles) and computational (yellow squares) techniques. Error bars stand for subject variability in all cases. inter-subject variability in all cases. Table 2 shows the slopes of the linear fittings of the chromatic difference of focus Table 2 shows the slopes of the linear fittings of the chromatic difference of focus curves for all IOLs and visual distances. The computational ray tracing and on bench, curves for all IOLs and visual distances. The computational ray tracing and on bench, which account only for the LCA of the IOL, data showed negative slopes for near vision, which account only for the LCA of the IOL, data showed negative slopes for near vision, but the experimental data in patients did not. but the experimental data in patients did not. Table 2. Slopes of the linear fittings of the chromatic difference of focus curves for all conditions and IOLs. Computational On Bench In Vivo Ray Tracing Monofocal hydrophobic Far 0.0063 0.0033 0.0063 Monofocal hydrophilic Far 0.0054 0.0018 0.0054 Far 0.0044 0.0022 0.0044 MIOL hydrophobic Int 0.0034 0.0019 0.0029 Near 0.0008 −0.0033 0.0008 Far 0.0037 0.0042 0.0037 MIOL hydrophilic Int 0.0018 −0.0006 0.0011 Near −0.0007 −0.0051 0.0011 3.5. Pseudophakic Longitudinal Chromatic Aberration Figure 7 shows the average LCA for far vision (480–700 nm) for phakic and pseudo- phakic eyes with subjective (solid gray bars) and computational (solid yellow bars) meth- ods. LCA in phakic and pseudophakic eyes obtained with the different techniques showed the same trends with higher values for subjective than computational LCA. LCA with the hydrophobic material is slightly, but is significantly higher than with the hydrophilic ma- terial both in monofocal and trifocal IOLs for far vision, with values of the same order of magnitude or lower than LCA in the phakic eye. For monofocal IOLs, computational ray tracing predictions matched results for hydrophobic, but differed slightly for hydrophilic lenses. For MIOLs, predictions matched the experimental LCA perfectly, but were higher than the experimental results in the hydrophobic case. In this particular case, computa- tional LCA for far vision is similar to that of the monofocal IOL with the same material. Photonics 2022, 9, 226 11 of 16 Table 2. Slopes of the linear fittings of the chromatic difference of focus curves for all conditions and IOLs. Computational On Bench In Vivo Ray Tracing Monofocal hydrophobic Far 0.0063 0.0033 0.0063 Monofocal hydrophilic Far 0.0054 0.0018 0.0054 Far 0.0044 0.0022 0.0044 MIOL hydrophobic Int 0.0034 0.0019 0.0029 Near 0.0008 0.0033 0.0008 Far 0.0037 0.0042 0.0037 MIOL hydrophilic Int 0.0018 0.0006 0.0011 Near 0.0007 0.0051 0.0011 3.5. Pseudophakic Longitudinal Chromatic Aberration Figure 7 shows the average LCA for far vision (480–700 nm) for phakic and pseudopha- kic eyes with subjective (solid gray bars) and computational (solid yellow bars) methods. LCA in phakic and pseudophakic eyes obtained with the different techniques showed the same trends with higher values for subjective than computational LCA. LCA with the hydrophobic material is slightly, but is significantly higher than with the hydrophilic material both in monofocal and trifocal IOLs for far vision, with values of the same order of magnitude or lower than LCA in the phakic eye. For monofocal IOLs, computational ray tracing predictions matched results for hydrophobic, but differed slightly for hydrophilic lenses. For MIOLs, predictions matched the experimental LCA perfectly, but were higher Photonics 2022, 9, x FOR PEER REVIEW 12 of 17 than the experimental results in the hydrophobic case. In this particular case, computational LCA for far vision is similar to that of the monofocal IOL with the same material. Figure 7. Average LCA (480–700 nm) for far vision for phakic and pseudophakic eyes obtained Figure 7. Average LCA (480–700 nm) for far vision for phakic and pseudophakic eyes obtained from from subjective (solid gray bars) and computational (solid yellow bars) methods for far vision. subjective (solid gray bars) and computational (solid yellow bars) methods for far vision. ** Highly ** statist Highly ically sig statistically nificant ( significant p < 0.01) differences between conditions (p < 0.01) differences between. Error bars indica conditions. Error te inte bars r-subject indicate variability. inter-subject variability. Figure 8 shows the average multifocal LCA for hydrophobic and hydrophilic MIOLs Figure 8 shows the average multifocal LCA for hydrophobic and hydrophilic MIOLs for far, intermediate, and near vision obtained with subjective (gray bars) and computa- for far, intermediate, and near vision obtained with subjective (gray bars) and computa- tional techniques (yellow bars). LCA decreases for intermediate and near vision in MIOLs tional techniques (yellow bars). LCA decreases for intermediate and near vision in MIOLs with similar results with all techniques. Simulations predicted subjective LCA well, with with similar results with all techniques. Simulations predicted subjective LCA well, with statistically significant differences only for MIOL hydrophilic in near vision. statistically significant differences only for MIOL hydrophilic in near vision. Figure 8. Average LCA (480–700 nm) for multifocal vision for hydrophobic and hydrophilic MIOLs from subjective (solid gray bars) and computational (solid yellow bars) methods for far, intermedi- ate, and near vision. Error bars stand for inter-subject variability in all cases. ** Statistically signifi- cant (p < 0.01) differences between conditions. Error bars indicate inter-subject variability. 4. Discussion Optical quality of multifocal IOLs is typically evaluated computationally using com- puter model eyes and on bench using optical quality metrics. Moreover, many studies have reported through-focus optical and visual quality in in vivo in patients implanted with multifocal IOLs, using Visual Strehl Ratio and Visual Acuity through-focus (defocus curves). The Visual Strehl ratio calculated from the combined wave aberrations have been shown to correlate well with visual acuity [57,58]. In particular, the defocus determined psychophysically appears to be captured well by the offset of the Visual Strehl peak [11,60], except for bias in the perceived best focus encountered in several refractive pro- files, particularly astigmatic patients [61]. However, differences between on bench and in vivo data have been previously reported, without a clear reasoning behind them. In our study, we found a good correspondence between the positions of the peaks of the through-focus curves (best focus) and the computational predictions of those peaks at far, Photonics 2022, 9, x FOR PEER REVIEW 12 of 17 Figure 7. Average LCA (480–700 nm) for far vision for phakic and pseudophakic eyes obtained from subjective (solid gray bars) and computational (solid yellow bars) methods for far vision. ** Highly statistically significant (p < 0.01) differences between conditions. Error bars indicate inter-subject variability. Figure 8 shows the average multifocal LCA for hydrophobic and hydrophilic MIOLs for far, intermediate, and near vision obtained with subjective (gray bars) and computa- tional techniques (yellow bars). LCA decreases for intermediate and near vision in MIOLs Photonics 2022, 9, 226 12 of 16 with similar results with all techniques. Simulations predicted subjective LCA well, with statistically significant differences only for MIOL hydrophilic in near vision. Figure 8. Average LCA (480–700 nm) for multifocal vision for hydrophobic and hydrophilic MIOLs Figure 8. Average LCA (480–700 nm) for multifocal vision for hydrophobic and hydrophilic MIOLs from subjective from subjective (solid gray bars (solid gray bars)) and compu and computational tational (so (solid lid y yellow ellow bars) me bars) methods thods for far, i for far, intermediate, ntermedi- ate, and near vision. Error bars stand for inter-subject variability in all cases. ** Statistically signifi- and near vision. Error bars stand for inter-subject variability in all cases. ** Statistically significant cant (p < 0.01) differences between conditions. Error bars indicate inter-subject variability. (p < 0.01) differences between conditions. Error bars indicate inter-subject variability. 4. Discussion 4. Discussion Optical quality of multifocal IOLs is typically evaluated computationally using com- Optical quality of multifocal IOLs is typically evaluated computationally using com- puter model eyes and on bench using optical quality metrics. Moreover, many studies have puter model eyes and on bench using optical quality metrics. Moreover, many studies reported through-focus optical and visual quality in in vivo in patients implanted with have reported through-focus optical and visual quality in in vivo in patients implanted multifocal IOLs, using Visual Strehl Ratio and Visual Acuity through-focus (defocus curves). with multifocal IOLs, using Visual Strehl Ratio and Visual Acuity through-focus (defocus The Visual Strehl ratio calculated from the combined wave aberrations have been shown to curves). The Visual Strehl ratio calculated from the combined wave aberrations have been correlate well with visual acuity [57,58]. In particular, the defocus determined psychophys- shown to correlate well with visual acuity [57,58]. In particular, the defocus determined ically appears to be captured well by the offset of the Visual Strehl peak [11,60], except psychophysically appears to be captured well by the offset of the Visual Strehl peak for bias in the perceived best focus encountered in several refractive profiles, particularly [11,60], except for bias in the perceived best focus encountered in several refractive pro- astigmatic patients [61]. However, differences between on bench and in vivo data have files, particularly astigmatic patients [61]. However, differences between on bench and in been previously reported, without a clear reasoning behind them. In our study, we found a vivo data have been previously reported, without a clear reasoning behind them. In our good correspondence between the positions of the peaks of the through-focus curves (best study, we found a good correspondence between the positions of the peaks of the focus) and the computational predictions of those peaks at far, intermediate and near in through-focus curves (best focus) and the computational predictions of those peaks at far, red light, and far and intermediate at all wavelengths with the hydrophobic lens, but there appears to be a systematic shift of the positions of the intermediate and near (towards less addition) in the real eye with respect to predicted values (Figure 6). Potential reasons for this discrepancy can be a broadening of the intermediate and near peaks, particularly in the presence of other aberrations, which challenges finding a clear peak. The lower addition, in terms of the difference between the CDF curves at the different distances, by 0.2 D at inter- mediate (hydrophobic) and 0.40/0.75 D at near (hydrophilic/hydrophobic), with respect to predicted by simulations and on-bench values is yet to be understood. Possible ways to test these hypotheses would involve measuring through-focus VA curves at different wavelengths, to assess not only the position of the peaks but the overall curve shape. Ad- ditionally, the models could be further sophisticated, including corneal aberrations of the patients, and account for potential shifts of the intermediate and near peaks in the presence of high order aberrations. Several refractive parameters, including spherical refractive error and astigmatism (with-the-rule or against-the-rule), may also affect perceptual setting of best focus, both in a young and a presbyopic population. We found that experimental chromatic difference of focus (slopes and LCA) predicted by simulations in computer eye models matches well the experimental findings (Figure 5). The slight discrepancy between experimental subjective LCA and the computer eye model simulation in the phakic eye for red light is similar to that the one obtained with other water eye models, such us the Indiana chromatic reduced eye model [62], where the Abbe number is adjusted to fit the psychophysical data. In a previous study [11], we showed that this chromatic eye model fitted the psychophysical data well for shorter wavelengths and the reflectometric data for longer wavelengths, with a general good agreement with data in shorter ranges from previous studies, both psychophysical and reflectometric. The Indiana chromatic reduced eye model, built using experimental data [63], predicts a chromatic Photonics 2022, 9, 226 13 of 16 focus shift of 1.00 D for VIS (480–700 nm), in agreement with the computational eye model predictions for the same range (1.10 D), and reflectometric objective measurements (Aerial imaging 0.95 D and Wavefront sensing 0.90 D), but lower than the experimental subjective LCA (1.52 D). The correction of high order aberrations did not alter those differences [11]. Experimental on bench [1,38] and in vivo in pseudophakic eyes [15,48,49] consistently indicate lower slopes and lower LCA values with hydrophilic than with hydrophobic materials. These results are consistent with the higher Abbe number in hydrophilic IOLs (58), followed by that of the natural eye (45) and that of hydrophobic IOLs (42). Furthermore, other on-bench studies [32,43–46] compared the optical performance of diffractive M- IOLs with visible and near infrared light, showing a bias in the optical performance of IOL towards far focus for near infrared illumination. Simulations predict the chromatic difference of focus curves for the monofocal hydrophobic IOL well, but show a significant discrepancy for monofocal hydrophilic IOLs in the blue region. As expected, patients implanted with multifocal IOLs with diffractive designs exhibit decreased slopes in the chromatic defocus curves and decreased LCA for intermediate and near with respect to those for far (Figure 7). This finding is consistent in both computer simulations and experimental subjective data in patients, for both hydrophilic and hy- drophobic materials. It is also consistent with on bench results for the isolated IOL (Gatinel et al. [1]), which showed negative slopes in chromatic defocus curves (and negative LCA) at near, due to the compensation of the IOL refractive LCA with the diffractive component. Simulations predict pseudophakic LCA well in vivo in all conditions, except for the hy- drophilic MIOL in near vision, where predictions show a more negative LCA than that of the experimental measurements (0.15 D vs. 0.13 D). This is probably due to the fact that simulations do not include, in this particular case, the effect of other ocular aberrations that might counteract the negative chromatic aberration induced by the multifocal diffractive design [64,65]. Nevertheless, the variability in the error setting is small in all cases at far (0.05–0.10 D), except for multifocal hydrophilic IOLs (0.37 D). 5. Conclusions Diffractive multifocal intraocular lenses modulate chromatic aberration and reduce it at certain distances due to interactions of refractive and diffractive chromatic components, displacing the position and peak magnitude of the foci at different visual distances, and even reversing chromatic aberration at some distances. Predicted differences due to the material and designs of the IOLs are confirmed by the experimental data (on bench and in vivo). Patients implanted with multifocal IOLs with diffractive designs exhibit decreased LCA at intermediate and near distances with respect to those at far, consistent with both computer simulations and experimental data, for both hydrophilic and hydrophobic materials. We demonstrate that experimental chromatic difference of focus (slopes and LCA) predicted by simulations in computer eye models matches the experimental findings well. We found a good correspondence between the positions of the peaks of the through-focus curves (best focus) and the computational predictions of those peaks at far, intermediate, and near vision. Computational ray tracing and on bench measure- ments allow for evaluating in vivo chromatic aberration with different materials and designs of multifocal diffractive intraocular lenses. Author Contributions: Study concept and design, S.M., C.D. and M.V.-P.; data collection, M.V.-P., A.G.-R., A.d.C. and N.G.; computational analysis, A.d.C.; on bench measurements, N.W. and S.R.; analysis and interpretation of data, S.M., A.d.C. and M.V.-P.; writing the manuscript, S.M. and M.V.-P.; administrative, technical, and material support, M.V.-P. and S.M.; supervision, M.V.-P. and S.M.; funding acquisition, S.M. All authors have read and agreed to the published version of the manuscript. Funding: This research received funding from the European Research Council under the ERC- 2011-AdG-294099 to S.M. and the H2020-MSCA-IF-GF-2019-MYOMICRO-893557 to M.V.-P.; the Spanish Government grant FIS2017-84753 and PID2020-115191RB-I00 to S.M., and collaborative Photonics 2022, 9, 226 14 of 16 agreements (2014–2020) with PhyIOL (Liege, Belgium), the National Eye Institute P30 Core Grant EY001319-46 (Center for Visual Science), and Unrestricted grant Research to Prevent Blindness (Flaum Eye Institute). Institutional Review Board Statement: All protocols met the tenets of the Declaration of Helsinki and were approved by the Spanish National Research Council (CSIC) Bio-ethical Committee. Informed Consent Statement: All participants were acquainted with the nature and possible conse- quences of the study and provided written informed consent. Data Availability Statement: All data generated or analyzed during this study are included in this published article. 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