Patient-centered and visual quality outcomes of premium cataract surgery: a systematic review

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1 EJO ISSN Eur J Ophthalmol 2017; 00 (00): DOI: /ejo REVIEW Patient-centered and visual quality outcomes of premium cataract surgery: a systematic review Sophia Y. Wang, Maxwell S. Stem, Gale Oren, Roni Shtein, Paul R. Lichter Department of Ophthalmology, Kellogg Eye Center, University of Michigan, Ann Arbor, MI - USA Abstract Purpose: Over 8 million cataract surgeries are performed in the United States and the European Union annually, with many patients choosing to pay out of pocket for premium options including premium intraocular lens implants (IOLs) or laser-assisted cataract surgery (LACS). This report provides a systematic review evaluating patientcentered and visual quality outcomes comparing standard monofocal IOLs to premium cataract surgery options. Methods: PubMed and EMBASE were searched for publications published between January 1, 1980, and September 18, 2016, on multifocal, accommodative, and toric IOLs, monovision, and LACS, which reported on 1) dysphotopsias, 2) contrast sensitivity, 3) spectacle, 4) vision-related quality of life or patient satisfaction, and 5) IOL exchange. Results: Multifocal lenses achieved higher rates of spectacle compared to monofocal lenses but also had higher reported frequency of dysphotopsia and worse contrast sensitivity, especially with low light or glare. Accommodative lenses were not associated with reduced contrast sensitivity or more dysphotopsia but had only modest improvements in spectacle compared to monofocal lenses. Studies of monovision did not target a sufficiently myopic outcome in the near-vision eye to achieve the full potential for spectacle. Patients reported high levels of overall satisfaction regardless of implanted IOL. No studies correlated patient-reported outcomes with patient expectations. Conclusions: Studies are needed to thoroughly compare patient-reported outcomes with concomitant patient expectations. In light of the substantial patient costs for premium options, patients and their surgeons will benefit from a better understanding of which surgical options best meet patients expectations and how those expectations can be impacted by premium versus monofocal including monovision options. Keywords: Accommodative IOL, Cataract surgery, Monovision, Multifocal IOL, Patient-reported outcomes, Patient satisfaction Introduction Nearly 4 million cataract surgeries are performed in the United States (1) and over 4 million cataract surgeries in the European Union (2) yearly. Standard cataract surgery replaces the cataract with a monofocal intraocular lens (IOL), allowing patients to see sharply at a single predetermined distance. However, postoperatively, most patients will still require spectacle correction some or all of the time (3). Some patients who strongly desire freedom from spectacles with standard monofocal implants will opt for a monovision strategy, where one eye is implanted with an IOL with a dioptric Accepted: April 4, 2017 Published online: April 24, 2017 Corresponding author: Paul R. Lichter, MD, MS W.K. Kellogg Eye Center 1000 Wall Street Ann Arbor, MI, USA plichter@med.umich.edu power providing clear distance vision, and the other eye is implanted with an IOL powered for clear near vision. The putatively uniform desire for spectacle-free vision following cataract surgery has paved the way for development of premium IOLs that patients may pay for out of pocket. Premium IOLs include monofocal toric lenses to correct astigmatism and multifocal and accommodative lenses meant to provide clear vision at near and distant focal points without additional spectacle correction. Table I summarizes characteristics of common multifocal and accommodative IOLs now or previously available worldwide. Multifocal lenses are either refractive or diffractive; refractive multifocal IOLs have ring-shaped or less commonly sector-shaped optical zones with differing dioptric powers, whereas diffractive multifocal IOLs have concentric stepped rings that use the optical principles of diffraction to focus light rays at multiple focal points. The earliest widely available refractive IOL was the Array, which was superseded by the Re- Zoom. Diffractive multifocal lenses that have been available in the United States for some time include the ReSTOR and Tecnis lenses. Tecnis Symfony is designed to provide a continuous range of focus across an extended range of distances,

2 2 Patient-centered and visual quality outcomes TABLE I - Selected multifocal and accommodative intraocular lens models Model Manufacturer FDA Materials Optics and properties Refractive multifocal Array ReZoom Domilens Progress TrueVista Lentis Mplus Diffractive AcrySof ReSTOR CeeOn 808X, 811X Tecnis Tecnis Symfony Acri.LISA 366D AT LISA tri 839MP Twin Set AMO (Santa Ana, CA, USA) Abbott Medical (Santa Ana, CA, USA) Bausch & Lomb (Claremont, CA, USA) Bausch & Lomb (Claremont, CA, USA) Oculentis GmbH (Berlin, Germany) Alcon (Fort Worth, TX, USA) Pharmacia Upjohn (Kalamazoo, MI, USA Abbott Medical (Santa Ana, CA, USA) Abbott Medical (Santa Ana, CA, USA) Carl Zeiss MediTec (Jena, Germany) Carl Zeiss Meditec (Jena, Germany) AcriTec (Henningsdorf, Germany) 1997 Three-piece silicone Zonal progressive with continuous power distribution on anterior surface; distance dominant, +3.5 D add; discontinued 2005 Acrylic with PMMA haptics Successor to Array lens; 5 concentric zones, with central distance and surrounding annular zones alternating between near and distance One-piece PMMA Central 4.7 mm anterior surface of progressively increasing power to a final add of D or +5.0 D, surrounded by an annular distance ring PMMA Bifocal with 3 zones: central distance, near annulus with +4.0 D add, peripheral distance; discontinued Hydrophilic acrylic with hydrophobic surface Rotationally asymmetric, with sector-shaped +3.0 add zone 2005 One-piece PMMA 3.6 mm diameter central apodized diffractive zone, available initially in +3.0 D (SN6AD1) and +4.0 D (SN6AD3), more recently +2.5 D (SV25T0) One-piece PMMA Bifocal; +4.0 D add; early model that became the basis of the Tecnis lens 2009 Three-piece silicone or hydrophobic acrylic Initial model of the Tecnis lens was the silicone ZM900 with +4.0 D add; now available in hydrophobic acrylic with D (ZKB00), D (ZLB00), +4.0 D (ZMB00) 2016 Hydrophobic acrylic New Tecnis model; concentric diffractive echelettes designed with extended range of focus rather than discrete separate focal points Hydrophilic acrylic (25%) with Bifocal; D add hydrophobic surface Hydrophilic acrylic (25%) with Trifocal; D near add, D intermediate hydrophobic surface add Three-piece silicone or platehaptic PMMA A set of 2 IOLs, with distribution of light such that 70% of the light is distributed to distance and 30% to near in one eye, and vice versa in the other eye; +4.0 D add FineVision PhysIOL (Belgium) Hydrophilic acrylic (25%) Trifocal; D near add and D intermediate add Accommodative 1CU Human Optics AG Hydrophilic acrylic Flexible plate-haptic design (Erlangen, Germany) Crystalens Bausch & Lomb (Claremont, CA, USA) 2003 Silicone Flexible plate-haptic; first and only FDA-approved accommodating IOL Tetraflex LensTec (St. Petersburg, FL, USA) Hydrophilic acrylic Flexible loop-style or open plate haptic design; underwent FDA trials but not yet approved Synchrony Lumina Visiogen, Abbott Medical Optics, AMO (Santa Ana, CA, USA) Akkolens/Oculentis (Breda, Netherlands) Silicone Year of approval is given if the lens is approved for use in the United States. FDA = Food and Drug Administration. Dual optic, 5.5-mm-high plus anterior optic (+32 D) with a 6-mm variable negative posterior optic; optics are connected by spring haptics; discontinued Sliding optics, designed to provide ~4 D of accommodating power, placed in the sulcus plane with haptics resting on the ciliary body; not yet approved

3 Wang et al 3 rather than discrete focal points corresponding only to near and distance. Accommodative IOLs are theoretically designed to dynamically transform from far to near focus by relying upon movement within the patient s eye during attempted accommodation. Of these, the more popular Crystalens and 1CU lenses are designed with hinged haptics, potentially allowing the optic-haptic complex to flex in response to accommodation and thereby change position and effective lens power within the eye. Premium lenses as well as a premium surgical option, laserassisted cataract surgery (LACS), are paid for out of pocket by the patient. In the United States, premium IOLs cost the patient an average of $2,000 (4, 5) per eye and can range up to $5,000 per eye (5). In Europe, the cost to the patient is typically less, but still poses a barrier to access (6, 7). By nature of their complex optical design, which splits incoming light beams into simultaneous different targets, multifocal lenses may cause a decrease in visual quality from disabling glare and halos and reduction in contrast sensitivity (8). With these potentially disabling side effects as a tradeoff for the hopedfor higher likelihood of freedom from glasses, it is imperative to compare overall patient-reported and visual quality outcomes between premium lens options and standard lens options, including monovision, to guide patients and physicians in their surgical choices. The aim of this report is to provide a systematic review of the literature comparing patientcentered and visual quality outcomes between premium IOL options and standard monofocal implants as well as LACS among adult patients undergoing cataract surgery. The main outcomes of interest were focused on vision quality, visionrelated quality of life, dysphotopsias, contrast sensitivity, spectacle, patient expectations, and patient satisfaction. Methods Search methods, eligibility criteria, and study selection PubMed and EMBASE databases were searched for articles published between January 1, 1980, and September 18, 2016, on multifocal, accommodative, and toric IOLs, monovision, and LACS, reporting on the following outcomes: 1) dysphotopsias; 2) contrast sensitivity; 3) spectacle ; 4) quality of life, functional outcomes, patient expectations, and patient satisfaction; and 5) IOL exchange. The full search strategy for PubMed and EMBASE is available in Appendix A and B, respectively. This search yielded 1,075 results from PubMed and 681 results from EMBASE (Fig. 1). After duplicates were excluded, 1,288 abstracts were reviewed by 2 independent reviewers for the following exclusion criteria: 1) not in English; 2) subjects not human; 3) any subjects under age 18; 4) less than 10 eyes per comparison group; 5) focused on special populations or complex cataract surgery (e.g., after trauma, post laser-assisted in situ keratomileusis); 6) evaluated clear lens extraction or refractive lens exchanges; 7) focused on microcoaxial phacoemulsification or associated IOLs; 8) focused on preoperative planning methods or equipment; 9) primarily a safety study (e.g., evaluating endophthalmitis, capsular tears); 10) did not include one of the above-mentioned outcomes (e.g., focused instead on modulation transfer function, retinal straylight, toric rotational stability); 11) did not evaluate a premium lens option (e.g., evaluated aspheric vs nonaspheric lenses); or 12) was not about cataract surgery (e.g., publications on multifocal choroiditis). A total of 899 publications were excluded at this stage. Full text of the remaining 389 publications was reviewed, of which a further 64 were excluded based on the same criteria, yielding a final number of 325 included publications (Fig. 1). Disagreement between reviewers was resolved by discussion. Data collection, risk of bias assessment, and analysis Included papers were categorized into different levels of evidence according to study design for risk of bias assessment. Categories included 1) meta-analyses, defined as studies that undertook a quantitative analysis or synthesis of data previously published in other original research studies; 2) randomized controlled trials (RCTs), in which participants must have been randomly assigned to receive a premium option vs standard surgery, with or without masking of the participants or evaluators; 3) case-control or cohort studies with a control (also includes nonrandomized trials), in which there was at least one group of participants who underwent a standard cataract surgery that could serve as a control; 4) any study design without such a control group; and 5) cost-effectiveness analyses in which the primary analyses concerned cost. Authors declared conflicts of interest were reviewed in studies categorized as meta-analyses, RCTs, case-control or cohort-controlled studies, or cost analyses. Categories of potential conflicts of interest included 1) no mention of any conflicts in the full-text article, 2) authors declared explicitly to have no conflicts of interest, and 3) authors declared to have related industry associations for example, consultant or advisor to a company manufacturing the intraocular lens being evaluated or the study was declared to be directly sponsored by industry. Results of studies that evaluated overall patient satisfaction, spectacle, contrast sensitivity, or dysphotopsias were reviewed and found to favor the premium cataract surgery option, favor the standard monofocal option (including monovision), or have no difference. For studies with multiple measures of dysphotopsias (e.g., patients reported both glare and halos) or multiple measures of contrast sensitivity under different conditions, results were judged to be in favor of monofocal lenses if any measure of dysphotopsia or contrast sensitivity was reported to be worse in the premium cohort. For spectacle and patient satisfaction, only the results of overall spectacle and overall patient satisfaction were considered. Fisher exact test was used to evaluate the relationship between conflicts of interest and results of studies. Results Results of the search The 325 articles eligible for inclusion were categorized according to different levels of evidence based on study

4 4 Patient-centered and visual quality outcomes Fig. 1 - PRISMA flow diagram of included and excluded studies. design (Tab. II). Studies that included a control group comprising patients who underwent standard cataract surgery included 8 meta-analyses, 26 RCTs, and 93 case-control or cohort-controlled studies. The remaining studies included 7 cost-effectiveness analyses and 191 studies that did not have a control or comparison group of patients who underwent a standard monofocal cataract surgery. Refractive and diffractive multifocal lenses We found 20 RCTs that compared multifocal to monofocal IOLs on dysphotopsias, contrast sensitivity, spectacle, or patient satisfaction and quality of life (Tab. III). TABLE II - Level of evidence and study design No. % Meta-analysis Randomized controlled trial Case-control, or cohort study with a control, in which at least one control group comprised a standard monofocal cataract surgery option Any study design without a control group comprising a standard monofocal cataract surgery option Cost-effectiveness analyses Total 325

5 Wang et al 5 TABLE III - Outcomes of randomized controlled trials evaluating multifocal intraocular lenses (IOLs) compared to standard monofocal IOLs Authors Journal Year IOL Dysphotopsias Contrast sensitivity Spectacle Steinert et al (39) Percival et al (100) Rossetti et al (20) Allen et al (40) Haaskjold et al (41) Javitt et al (21) Javitt et al (19) Kamlesh et al (22) Ophthalmology 1992 Array Regan, multifocal lower than monofocal at lowest level of contrast tested J Cataract Refract Surg J Cataract Refract Surg J Cataract Refract Surg J Cataract Refract Surg J Cataract Refract Surg 1993 Array Regan, multifocal lower than monofocal at lowest level of contrast tested M Glare: 7 (45%) multifocal vs 8 (19%) monofocal; halos 22 (58%) multifocal vs 5 (12%) monofocal; no statistics reported 1996 CeeOn 808X 1998 CeeOn 808X 2000 Array Halos: 41.4% multifocal vs 2% monofocal with halos (p<0.001); glare: self-reported; no difference for most activities, except multifocal reported less limitation from glare when reading text on shiny paper and reading signs in supermarkets Ophthalmology 2000 Array Glare: no difference in any activities Can J Ophthalmol 2001 Domilens Progress 3 Glare: 9 (45%) multifocal vs 6 (30%) monofocal; halos: 3 (15%) multifocal vs 1 (5%) monofocal; no statistics performed VCTS, multifocal worse than monofocal at all spatial frequencies VCTS, multifocal worse than monofocal at all spatial frequencies Pelli-Robson; multifocal worse (p<0.001) 48% multifocal vs 8% monofocal were spectacleindependent (p = ) Satisfaction/ quality of life 26 (68.4%) multifocal vs 33 (78.5) monofocal satisfied or highly satisfied with quality of vision, nonsignificant trend 37.0% multifocal 85% multifocal and vs 6.0% monofocal reported com- rated overall vision 86% monofocal plete spectacle as good 41% multifocal vs 12% monofocal with spectacle (p<0.001) 32% multifocal vs 8% monofocal with spectacle (p<0.0001) 9 (45%) multifocal vs 19 (95%) monofocal need additional glasses for near work, no statistics Self-reported rating of vision higher in multifocals with and without glasses; multifocal less limited in reading a magazine, newspaper, or telephone book, crafts or hobbies, reading labels or prices, but no difference in depth perception, shaving, or putting on makeup Self-reported rating of vision higher in multifocals without glasses, but no significant difference with glasses; multifocals less limitation in reading a magazine, newspaper, or telephone book, crafts or hobbies, and reading labels or prices; no difference in depth perception, shaving, or putting on makeup 14 (70%) multifocal vs 16 (80%) monofocal good, no statistics To be continued

6 6 Patient-centered and visual quality outcomes TABLE III - Continued Authors Journal Year IOL Dysphotopsias Contrast sensitivity Spectacle Satisfaction/ quality of life Leyland et al (74) Nijkamp et al (18) Sen et al (17) Zeng et al (42) Cillino et al (12) Harman et al (43) Eye 2002 Array, TrueVista Degree of bother from glare, halo, or rings are light (TyPE questionnaire); multifocal group scored worse (p = 0.01) Ophthalmology 2004 Array Multifocals slightly higher on the cataract symptom score questionnaire (p = 0.002) J Cataract Refract Surg Clin Exp Ophthalmol 2004 Array Glare nonsignificant; halos 21 (40.5%) vs 5 (7.5%) (p<0.001) 2007 Array VCTS, multifocal worse than monofocal at all spatial frequencies Ophthalmology 2008 Array, ReZoom, Tecnis Glare nonsignificant; halos 0 reports in the monofocal compared to 7 (43.8%) Array (p = 0.007), 9 (60%) ReZoom (p = ), 2 (12.5%) Tecnis (nonsignificant) Ophthalmology CU, Array 16.7% multifocal vs 9.8% monofocal with moderate to severe glare at 18 months (p = 0.046) 7 (25%) multifocal vs 0 monofocal with complete spectacle No significant difference for overall satisfaction (8/10 for all IOLs) 29 (42.7%) multifocal vs 14 (21.6%) monofocal using no reading No significant differences in the VF-14, VQOL, overall patient satis- glasses or only faction. High overall wearing them now and then (significant) satisfaction with the quality of near vision with glasses (88.0% monofocal and 89.7% multifocal), compared with 49.2% monofocal and 61.8% multifocal without glasses VCTS, nonsignificant 50 (94.3%) multifocal vs 63 (93.9%) monofocal very satisfied or satisfied overall, nonsignificant VCTS, monofocal and Tecnis better than Array and ReZoom only at 3 cycles/degree Pelli-Robson; nonsignificant at 18 months 3 (20%) monofocal vs 7 (43.7%) Array, 8 (53.3%) ReZoom, 14 (87.5%) Tecnis with complete spectacle, all significant 6 (27.3%) Array vs vs 0 monofocal with complete spectacle (p = 0.001) VF-7 score lower in the monofocal group (87.1%) vs Array (93.8%), ReZoom (94.6%), Tecnis (99.1%), p = 0.002; multifocal groups with better scores than monofocal controls on reading small print and doing fine handwork without glasses (p = ), but no differences in driving at night, television watching, cooking; overall satisfaction no difference among the 4 groups To be continued

7 Wang et al 7 TABLE III - Continued Authors Journal Year IOL Dysphotopsias Contrast sensitivity Spectacle Martinez Palmer et al (16) Zhao et al (15) Peng et al (13) Ji et al (44) Gil et al (45) Shah et al (14) J Refract Surg 2008 Tecnis, ReZoom, TwinSet J Cataract Refract Surg Acta Ophthalmol Spontaneously reported dysphotopsia: none in the monofocal group compared to 16%-19% in multifocal IOL groups (p = 0.01) 2010 ReSTOR Halos: 31 (43.1%) multifocal vs 18 (20.2%) monofocal (p<0.01); glare nonsignificant 2012 ReSTOR Scores on glare/ flare, problems with night vision, halos all significantly higher in multifocal vs monofocal group VCTS; monofocal better than Tecnis under nearly all conditions, better than Twinset and ReZoom under select conditions VCTS, monofocal better at 3 cycles per degree (p<0.05) 4% monofocal compared to 87.5% TwinSet, 77% Tecnis (no. unknown), 14 (44%) ReZoom with total spectacle 37 (74.0%) multifocal vs 13 (28.9%) monofocal reported overall spectacle (p<0.001) at all spatial frequencies Exp Ther Med 2013 ReSTOR VCTS; monofocal better Eur J Ophthalmol 2014 ReSTOR, ReZoom, Tecnis J Refract Surg 2015 ReSTOR Glare dimension scores of the NEI RQL-42 worse in multifocal compared to monofocal (p<0.05) VCTS; monofocal better at all spatial frequencies Satisfaction/ quality of life 48 (66.6%) VF-7 score lower in multifocal vs the monofocal group 21 (23.5%) (89.8) vs multifocal (97.3) (p<0.05); multifocal achieved spectacle satisfaction no mean overall patient (p<0.05) difference Satisfaction higher in multifocal group (8.14) vs monofocal group (6.23) (p<0.001) 74 (73.3%) multifocal vs %) monofocal with spectacle (p<0.0001) IOL = intraocular lens; NEI RQL-42 = National Eye Institute Refractive Error Quality of Life Instrument; = not reported; VCTS = Vistech Vision Contrast Test System; VF-7 = Visual Function Index. Dysphotopsias Four meta-analyses provided pooled analyses comparing multifocal lenses to monofocal lenses on the outcome of dysphotopsias (8-11). Calladine et al (8) reported that patients with multifocal lenses had a higher risk ratio for reporting glare or halos (1.94, 95% confidence interval [CI] ). Cochener et al (10) reported no significant increase in the incidence rate ratio for halos in multifocal lenses compared to monofocal lenses. Eleven RCTs compared multifocal to monofocal IOLs and reported results on dysphotopsias (Tab. III) (12-22). Cillino et al (12) reported that the Array, ReZoom, and Tecnis ZM900 lenses were associated with significantly higher reports of halos than the monofocal control. Nighttime glare was worse in the refractive Array and ReZoom groups than the monofocal or Tecnis groups but there were no significant differences in overall glare. Martinez Palmer et al (16) reported that no patients implanted with monofocal IOLs spontaneously complained of dysphotopsias, compared to 16%-19% of patients implanted with multifocal IOLs; on a questionnaire specifically eliciting dysphotopsia reports, those in the Tecnis group had the highest frequency of dysphotopsia phenomena (81% vs 47%-53% in the monofocal and other multifocal groups). Trials evaluating the AcrySof ReSTOR have reported worse glare and halos (13), worse halos without significantly worse glare (15), or worse glare only (14) compared to monofocal lenses. Results of case-control and cohort-controlled studies also typically reported more severe or higher frequency of photic phenomena associated with multifocal lenses including halos and glare (23-26), or greater degree of bother and limitation in driving toward oncoming headlights due to glare and halos (27). Photic phenomena were reported to disappear in patients with monofocal IOLs at a higher rate over time (24). Studies of more modern lenses such as the Tecnis ZM900, ReZoom, and ReSTOR have also typically reported worse glare, worse halos, or both (28-34). A few studies found no

8 8 Patient-centered and visual quality outcomes difference in glare or halos between monofocal and multifocal lenses (35-37). One study reported no differences in glare symptoms between the Tecnis Symfony and monofocal lenses (38). Contrast sensitivity Contrast sensitivity is evaluated by several different methods, ranging from simple measures such as the Pelli-Robson chart to more complex measures involving sine-wave gratings with varying spatial frequencies, tested under varying lighting conditions (Vistech VCTS). Pooled results of 4 trials measuring contrast sensitivity using the Pelli-Robson chart did not reveal a significant difference in contrast sensitivity between monofocal and multifocal groups (8). Thirteen RCTs compared contrast sensitivity between multifocal and standard monofocal lenses (Tab. III) (12, 15-17, 22, 39-45, 100). Comparisons of monofocal lenses to the TwinSet, Tecnis, and ReZoom lenses under varying luminance conditions and at different spatial frequencies found a disadvantage for multifocal lenses under at least some conditions (16). Another study found that monofocal and Tecnis lenses were associated with better contrast sensitivity than the Array and ReZoom lenses but only at the lowest spatial frequency (12). Studies of the ReSTOR lens have also shown that it is associated with decreased contrast sensitivity compared to monofocal lenses, either at all spatial frequencies (44, 45) or in certain lower spatial frequencies (15). Results of the case-control and cohort with control studies were similar to those of the RCTs; most found some advantage in contrast sensitivity with monofocal lenses compared to multifocal lenses. Early studies of refractive and diffractive IOLs including the Array lens reported a reduction in contrast sensitivity compared to monofocal controls under most conditions (46-51), at the lower levels of Regan contrast conditions (26, 35, 52-54), low frequency (55), or under adverse testing conditions such as glare (56), low luminance (57), or low luminance with glare (58). One study of the Array lens suggested that patients have an initial reduction in contrast sensitivity that improves over time postoperatively, whereas the monofocal group achieved stable normal contrast sensitivity values early in the postoperative course (59). Studies of more recent lenses including the Acri.LISA 366D (60), ReSTOR, ReZoom (61, 62), and Tecnis (31, 60, 61, 63) also demonstrated that monofocal controls offered the best performance particularly under adverse conditions such as at lower contrast levels or under glare conditions (32, 33, 64) or lower spatial frequency (65), under photopic but not mesopic conditions (66), or under monocular but not binocular conditions (67). Only a few studies did not find any significant differences in contrast sensitivity between monofocal and multifocal Array (68), ReSTOR (32, 69-72), Tecnis (73), or Lentis M-Plus lenses (60). One study of the Tecnis Symfony reported no differences in contrast sensitivity between the Symfony and the monofocal control at any spatial frequency (38). Spectacle Five meta-analyses addressed the issue of spectacle between multifocal IOLs and monofocal IOLs (8, 10, 11, 74, 75). Calladine et al (8) reported that multifocal IOLs were associated with much lower chance of spectacle dependence compared to monofocal IOLs (risk ratio (RR) 0.60, 95% CI ). Cochener et al (10) reported that multifocal IOLs were associated with significantly increased incidence of spectacle overall compared to monofocal IOLs (incidence rate ratio (IRR) 3.62, 95% CI ). We found 13 RCTs that compared spectacle between patients with multifocal or monofocal IOLs (Tab. III) (12-16, 18-21, 40, 43, 49, 74). Most studies reported improved spectacle for recipients of multifocal lenses, particularly for near tasks (16, 20, 40, 49, 74). Trials evaluating the Array lens found that 27%-42.7% were spectacle independent in the Array group compared to 0%-21.6% of monofocal control groups (12, 18, 19, 43, 74). Two studies also compared monofocal lenses to both Tecnis and ReZoom lenses, reporting the highest rate of spectacle with the Tecnis lens (77%-87.5%) and a lower rate of spectacle with the ReZoom lens (44%- 53.3%), compared to 4%-20% spectacle in monofocal control groups (12, 16). Trials of the ReSTOR lens reported 66.6%-73.3% spectacle with the ReSTOR compared to 23.5%-25.3% in the monofocal group (13, 15). Results of the case-control and cohort control studies also showed that a significantly higher percentage of patients implanted with multifocal IOLs were spectacle independent overall or at near compared to monofocal lenses. Spectacle at near for early multifocal IOLs ranged from 38.4% to 86% in multifocal groups compared to 9.8%-32% of monofocal groups (26, 27), with overall or distance spectacle ranging from 81.3% to 84.9% for multifocal lenses vs 52.4%-85% for monofocal lenses (26, 68). Studies of the ReSTOR reported overall spectacle rates ranging from 80% to 92% in the ReSTOR compared to 7.5%-12% of comparison monofocal lenses (29, 30, 76) and spectacle rates at near ranging from 81% to 100% in multifocal patients compared to 2.9%-16.7% in monofocal patients (30, 33, 64, 77). Studies of the Tecnis ZM900 report a similar range of 86.4%-96.4% of patients with spectacle for near compared to 12.5%-30.4% of monofocal patients (34, 63, 73). One study reported that patients implanted with the Tecnis Symfony reported overall less dependence on spectacle correction compared to patients implanted with monofocal lenses (38). Patient satisfaction and quality of life outcomes Thirteen RCTs addressed the outcome of patient satisfaction or quality of life, summarized in Table III (12, 13, 15, 17-22, 40, 74). Studies varied greatly in methods of measuring patient satisfaction or quality of life. Most studies found very high levels of overall satisfaction among both patients with multifocal and monofocal lenses (22, 40). Some studies reported some advantages with satisfaction or performance at near (20), particularly without glasses (19). Many studies (12, 17, 18, 74) did not find any differences compared to monofocal lenses in overall patient satisfaction, which was uniformly high. Zhao et al (15) reported higher Visual Function Index (VF)-7 scores in the ReSTOR group compared to the monofocal

9 Wang et al 9 control group (97.3 vs 89.8, p<0.05) but no significant difference in mean overall patient satisfaction score. However, Peng et al (66) reported higher patient-reported satisfaction in the ReSTOR group compared to the monofocal control group (8.14 vs 6.23, p<0.001). Results of the case-control and cohort controlled studies were similar. One study reported that AcrySof ReSTOR patients reported higher satisfaction than a monofocal comparison group (p<0.001) (28), but more often, studies found that there were no differences between multifocal and monofocal satisfaction (29, 34, 49, 63). Two small early studies reported that patients who were implanted with a bifocal lens in one eye and a monofocal lens in the other more often preferred the monofocal eye (78, 79). Some studies differentiated between satisfaction with near vision or distance vision, near or distance tasks, or overall vision. Lehmann et al (30) reported a detailed analysis of patient-reported satisfaction and performance in a wide variety of near, distance, and social activities comparing the ReSTOR lens and conventional monofocal control. The ReSTOR group was significantly more satisfied with uncorrected near and distance vision, and reported less limitation in near vision activities, social activities, and certain distance vision activities including usual daily activities, daytime driving, and reading street signs. Most other studies reported that satisfaction with near vision or performance of near activities was better for ReSTOR compared to monofocal lenses, but did not find differences in satisfaction with distance vision or performance of distance activities (29, 33, 67, 80). One study reported that VF-14 scores were significantly higher in patients implanted with ReSTOR lenses compared to patients implanted with monofocal lenses (66). One study of the Tecnis Symfony reported no difference in overall satisfaction with correction compared to monofocal control (38). Accommodative lenses Two RCTs compared the 1CU accommodative IOL to a monofocal control and addressed dysphotopsias, contrast sensitivity, or spectacle (Tab. IV) (43, 81). Both of these studies found no evidence of a loss in contrast TABLE IV - Outcomes of randomized controlled trials evaluating accommodative intraocular lenses (IOLs) and monovision Authors Journal Year IOL Aim Dysphotopsias Contrast sensitivity Accommodative vs standard monofocal Kamppeter et al (81) Harman et al (43) Alió et al (82) Monovision vs multifocal Wilkins et al (91) Labiris et al (90) Eur J Ophthalmol Ophthalmology CU, Array Am J Ophthalmol CU No significant differences Plano 4.8% of 1CU and 9.8% of monofocal group experienced moderate to severe glare at 18 months (p = 0.474) Kontrastometer BA4; no significant differences Pelli-Robson; no significant differences for 1CU compared to monofocal 2016 Lumina Topcon; no significant differences Ophthalmology 2013 Tecnis ZM900; monovision J Cataract Refract Surg 2015 Isert PY60MV, monovision IOL = intraocular lens; = not reported; VF = Visual Function Index. Plano for distance eye; -1 D to -1.5 D for the near eye (mean D achieved) D for the distance eye; for the near eye (mean D achieved) At least some Pelli-Robson; glare or dazzle monovision reported by 79% better than multifocal vs multifocal 56% (p = 0.009) monovision (p = 0.001) Glare: no significant differences; unwanted shadows more in multifocal group (p = 0.02) Pelli-Robson; no significant differences 19.0% of 1CU group vs 0% of the monofocals (p = 0.049) 24 (25.8%) monovision and 67 (71.3%) multifocal reported never wearing glasses Spectacle Satisfaction/quality of life 12 (31.4%) in VF-14 monovision scores no group and significant 26 (65.7%) in differences multifocal group were spectacle independent

10 10 Patient-centered and visual quality outcomes sensitivity compared to monofocal lenses, and no significant differences in glare. Harman et al (43) reported that 19.0% of the 1CU group were completely spectacle independent, compared to none of the monofocal group, and that a higher proportion of the monofocal group, 72.2%, required glasses for all reading tasks, compared with 23.8% of the 1CU group (p = 0.049). One RCT compared the Lumina lens to a monofocal and reported no difference in contrast sensitivity (82). Results from case-control and cohort-control studies were similar. Additional studies of the 1CU lens have also noted no differences in glare (34) or contrast sensitivity (61) and reported decreased spectacle dependence at near (61.9% 1CU vs 87.5% monofocal) (34) when comparing 1CU to monofocal lenses. One study of the Crystalens found no differences in contrast sensitivity compared to monofocal controls under a variety of conditions (83). One study of the Tetraflex lens also found no differences in contrast sensitivity (84), with 60% of the Tetraflex group achieving total spectacle, compared to 17.2% of the monofocal controls (84). A nonrandomized Food and Drug Administration trial of the Tetraflex reported that that 75% of Tetraflex patients reported wearing spectacles for near work never or only occasionally for small print or dim light, compared with 46% of control patients (85). Overall patient satisfaction for accommodative lenses has been reported to be high (90.4% satisfaction in 1CU vs 91.6% in monofocal) (34). Toric lenses We found very few studies comparing monofocal toric lenses to monofocal nontoric lenses with regard to patientcentered or visual quality outcomes. Reports of spectacle at distance for toric lenses was better than for monofocal nontoric control lenses, ranging from 61.0% to 97% compared to 31%-50%, respectively (86-88). Lane et al (87) reported that nearly all patients in both the nontoric and toric groups were either satisfied or very satisfied with their uncorrected distance vision in a variety of settings, with no statistical difference achieved between the groups. However, Mencucci et al (89) found that recipients of the toric IOL had higher scores on the NEI Refractive Error Quality of Life Instrument-42 questionnaire on the dimensions of clarity of vision, distance vision, glare, and satisfaction with correction compared to recipients of the nontoric control lens. Monovision Two trials compared monovision to multifocal lens implantation (Tab. IV). Labiris et al (90) compared the refractive multifocal Isert PY60MV against monovision with near target of D and found no differences in contrast sensitivity or glare between the 2 groups, but significantly more unwanted shadows in the multifocal group (90). A total of 31.4% of the monovision group achieved complete spectacle compared to 65.7% of the multifocal group. There was no significant difference in spectacle dependence at distance, but the multifocal group reported less spectacle dependence at near. Scores on the VF-14 did not differ for near vision, distance vision, or overall between the 2 groups (90). Wilkins et al (91) compared bilateral implantation of the Tecnis ZM900 multifocal lens against monovision with near aim of D. Contrast sensitivity was significantly reduced in the Tecnis group compared to the monovision group, and multifocal patients reported significantly more glare or dazzle (91). A total of 25.8% of the monovision group reported never wearing glasses, compared to 71.3% of the multifocal group; logistic regression modeling found that multifocal patients had over 650% higher odds of spectacle (odds ratio 7.51, 95% CI ) (91). However, despite the near refractive goal being D, the refractive results achieved were a mean D, which surely contributed to a higher reliance on spectacles for near work in this group. Overall satisfaction was similar between both groups (85% satisfied with monovision and 81% satisfied with multifocal) (91). However, 6 patients (5.7%) of the multifocal group underwent IOL exchange, of which 5 exchanges were due to patient dissatisfaction about image quality, compared to no IOL exchanges in the monovision group (91). Case-control and cohort-controlled comparisons of monovision with bilateral multifocal lens implantation have reported similar results. Two smaller studies reported spectacle ranging from 55% to 77% in monovision groups compared to 40% to 67% in the multifocal groups; differences were not statistically significant but the groups were approximately 20 patients in each case (92, 93). Zhang et al (92) reported significantly more glare and halos in the multifocal group compared to the monovision group but similar overall levels of satisfaction in both groups. One study compared monovision with bilateral implantation of Tetraflex or Crystalens accommodative lenses (94). The authors noted that manufacturers recommendations for dioptric target was followed, which for Tetraflex was D and D, and for Crystalens was D in both eyes. The monofocal monovision targets were and The authors did not find any significant differences among the 3 groups in distance or near acuities or contrast sensitivities, although they did not report data on spectacle (94). Laser-assisted cataract surgery Although we included in our search key words related to femtosecond laser-assisted cataract surgery, we did not find any publications that addressed patient-reported outcomes such as overall patient satisfaction, glare/halos/dysphotopsias, or contrast sensitivity. Conflicts of interest A review of the conflicts of interest was undertaken of the 134 studies that were meta-analyses, RCTs, other controlled studies, or cost analyses in order to investigate risk of bias in the literature. Of these, 32 (23.9%) did not include a conflict of interest disclosure statement, 66 (49.3%) were declared to be free of conflicts of interest, and the remaining 36 (26.9%) were directly sponsored by industry or included authors with related industry associations. Figure 2 depicts the relationship between conflicts of interest and whether the reported results of meta-analyses, RCTs, and nonrandomized controlled studies favored standard or premium cataract surgical options for each of the 4 outcomes of interest. Regardless of conflict of interest

11 Wang et al 11 Fig. 2 - Results of randomized controlled trials, meta-analyses, and non-randomized controlled studies by conflict of interest category. Included randomized controlled trials, meta-analyses, and non-randomized controlled studies were reviewed for conflict of interest disclosure statements. The studies were found to be declared free of conflicts of interest, or were industry-associated or industry-sponsored, or did not have a disclosure statement. Results of studies that evaluated overall patient satisfaction, spectacle, contrast sensitivity, or dysphotopsias were reviewed and found to favor the premium cataract surgery option, favor the standard monofocal option (including monovision), or have no difference. For studies with multiple measures of dysphotopsias (e.g., patients reported both glare and halos) or multiple measures of contrast sensitivity under different conditions, results were judged to be in favor of monofocal lens if any measure of dysphotopsia or contrast sensitivity was reported to be worse in the premium case. For spectacle and patient satisfaction, only the results of overall spectacle and overall patient satisfaction are depicted here, as opposed to only under specific conditions, e.g., satisfaction or spectacle at distance only or near only. category, most studies reporting results on dysphotopsias or contrast sensitivity favored the standard monofocal lens, and most studies reporting on results of overall spectacle favored the premium lens option. A higher proportion of industry-associated or industry-sponsored studies reported higher overall patient satisfaction for premium lenses, but this was not a statistically significant difference (p = 0.659, Fisher exact test). Discussion Multifocal lenses were associated with higher rates of spectacle than monofocal lenses, but were also more frequently associated with dysphotopsias and decreased contrast sensitivity. Accommodative lenses were not associated with increased dysphotopsias or decreased contrast sensitivity, but rates of spectacle were modest. Multifocal, accommodative, and monofocal lenses were all associated with high levels of overall patient satisfaction. Multifocal lenses were reported to achieve higher rates of spectacle compared to monovision. However, in these studies, the near vision refractive goal for the monovision group was likely too mildly myopic to provide clear near vision. Moreover, patients with multifocal lenses were found to be more likely than patients with monovision to undergo IOL exchange, due to dissatisfaction with image quality. The design of many multifocal lenses has evolved since the development and evaluation of the earliest models. Both the ReSTOR and the Tecnis IOLs now have a low-add model with D (ReSTOR) or D (Tecnis) of add power; the low-add Tecnis model has been demonstrated to achieve

12 12 Patient-centered and visual quality outcomes better spectacle, fewer visual symptoms, and higher patient satisfaction compared to older higher-add models (95) but has not been compared in RCTs to monofocal lenses. Thus, it is difficult to ascertain how these newer IOL models compare to standard monofocal implants, and whether they truly deliver acceptable visual quality and freedom from spectacles, as manufacturers often claim. Studies of the most recently approved Tecnis Symfony lens have suggested a higher degree of spectacle with the Symfony and no significant differences in contrast sensitivity or satisfaction, findings that will need to be borne out in future studies (38). This review also found that monovision as a strategy to achieve spectacle has not been adequately evaluated, which is especially relevant as monovision does not require additional out-of-pocket cost to the patient. By targeting a near refraction of only D to D and falling generally short of those targets, both trials that compared monovision to multifocal lenses failed to achieve an adequately myopic refraction, thus reducing the likelihood of achieving spectacle in those studies (90, 91). Most reviewed studies reported very high rates of satisfaction with both standard monofocal implants and premium lens options, though satisfaction and quality of life were measured using diverse methods. Nevertheless, it is undeniable that there exists a subset of patients implanted with multifocal lenses who are subsequently bothered by glare, halos, and reduced contrast sensitivity, sometimes to the point of pursuing additional surgery to exchange the IOL (91, 96-99). Surveys of cataract surgeons have reported that multifocal lenses constitute 6%-31% of all IOLs reported to be explanted and that the most common reason for explantation of these lenses was due to optical aberrations such as glare, halos, or dysphotopsias (96-99). It is often assumed that patients are motivated to achieve spectacle, but there is a lack of studies documenting patients goals for cataract surgery outcomes. Furthermore, measuring overall satisfaction on a simple scale ignores the nuances of how preoperative goals are discussed with the patient and how that may impact postoperative satisfaction. There is no universally accepted and standard validated measure of patient satisfaction after cataract surgery, and no measures that incorporate preoperative goals. Irrespective of which type of lens was implanted, patients who may not have understood the compromises of their choices could report high satisfaction with cataract surgery, not realizing that their quality of vision might have been better had they made a different choice. Since patients must decide whether to bear the burden of out-of-pocket costs for premium lenses, it is important to evaluate to what extent preoperative goals impact postoperative satisfaction in a nuanced way and with validated measures. Strengths of our study include its comprehensive search and inclusion of many studies, including nonrandomized studies for a more complete review of the literature. Information on studies conflicts of interest was reported for a novel perspective on possible bias within the literature. This study also evaluated all types of premium cataract surgery with several types of IOLs and multiple patient-reported outcomes. Conversely, with many different studies and study types that utilized diverse methods, means of outcome reporting, and types of lenses, it was not possible to pool results into summary measures. As mentioned above, many reviewed studies pertained to older models of intraocular lenses, which may limit their relevance to cataract surgery with more modern lenses. Conclusions Current literature confirms in multiple studies what one would expect empirically that premium cataract surgery lenses are more effective at providing spectacle than monofocal lenses. However, multiple studies also show that spectacle with multifocal IOLs risks the compromise of reduced contrast sensitivity and higher rate of dysphotopsias. Studies that assess patient goals for their cataract surgery outcomes are essential, especially the extent to which patients value the prospect of spectacle. In addition, evaluation of the predictors of overall postoperative satisfaction and quality of life will be important to aid cataract surgeons in performing appropriate preoperative patient evaluation and counseling, and aid individual patients in choosing the most personally beneficial cataract surgery option to optimize functional outcomes. Furthermore, there is a critical need to evaluate patient-centered outcomes of modern premium IOL models, since design evolution may impact contrast sensitivity, glare, halos, spectacle, and satisfaction. Comparison of these lenses against standard monofocal options including monovision with an efficacious near target will be important to determine the benefit of patient-pay premium cataract surgery options. Studies of patient-centered outcomes with LACS are also needed. Large studies with sufficient follow-up will allow for evaluation of uncommon but serious outcomes, such as IOL exchange due to dissatisfaction with visual quality. In conclusion, there is a need for large studies evaluating standard (including monovision) and premium cataract surgery options, from initial patient expectations to final patientreported and visual quality outcomes. Disclosures Financial support: No financial support was received for this submission. Conflict of interest: None of the authors has conflict of interest with this submission. References 1. Prevent Blindness America. Vision Problems in the U.S. Prevalence of Adult Vision Impairment and Age-Related Eye Diseases in America Eurostat. Surgical operations and procedures statistics. ec.europa.eu/eurostat/statistics-explained/index.php/surgical_ operations_and_procedures_statistics. Accessed February 18, Wilkins MR, Allan B, Rubin G. Spectacle use after routine cataract surgery. Br J Ophthalmol. 2009;93(10): Maxwell WA, Waycaster CR, D Souza AO, Meissner BL, Hileman K. A United States cost-benefit comparison of an apodized, diffractive, presbyopia-correcting, multifocal intraocular lens and a conventional monofocal lens. J Cataract Refract Surg. 2008;34(11):