Multifocal versus monofocal intraocular lenses after cataract extraction

ABSTRACT BACKGROUND: Good unaided distance visual acuity is now a realistic expectation following cataract surgery and intraocular lens (IOL) implantation. Near vision, however, still requires additional refractive power, usually in the form of reading glasses. Multiple optic (multifocal) IOLs are available which claim to allow good vision at a range of distances. It is unclear whether this benefit outweighs the optical compromises inherent in multifocal IOLs. OBJECTIVES: The objective of this review was to assess the effects of multifocal IOLs, including effects on visual acuity, subjective visual satisfaction, spectacle dependence, glare and contrast sensitivity, compared to standard monofocal lenses in people undergoing cataract surgery. METHODS: Search methods: We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register), The Cochrane Library 2012, Issue 2, MEDLINE (January 1946 to March 2012), EMBASE (January 1980 to March 2012), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. The electronic databases were last searched on 6 March 2012. We searched the reference lists of relevant articles and contacted investigators of included studies and manufacturers of multifocal IOLs for information about additional published and unpublished studies. Selection criteria: All randomised controlled trials comparing a multifocal IOL of any type with a monofocal IOL as control were included. Both unilateral and bilateral implantation trials were included. Data collection and analysis: Two authors collected data and assessed trial quality. Where possible, we pooled data from the individual studies using a random-effects model, otherwise we tabulated data. MAIN RESULTS: Sixteen completed trials (1608 participants) and two ongoing trials were identified. All included trials compared multifocal and monofocal lenses but there was considerable variety in the make and model of lenses implanted. Overall we considered the trials at risk of performance and detection bias because it was difficult to mask patients and outcome assessors. It was also difficult to assess the role of reporting bias. There was moderate quality evidence that similar distance acuity is achieved with both types of lenses (pooled risk ratio, RR for unaided visual acuity worse than 6/6: 0.98, 95% confidence interval, CI 0.91 to 1.05). There was also evidence that people with multifocal lenses had better near vision but methodological and statistical heterogeneity meant that we did not calculate a pooled estimate for effect on near vision. Total freedom from use of glasses was achieved more frequently with multifocal than monofocal IOLs. Adverse subjective visual phenomena, particularly haloes, or rings around lights, were more prevalent and more troublesome in participants with the multifocal IOL and there was evidence of reduced contrast sensitivity with the multifocal lenses. AUTHORS’ CONCLUSIONS: Multifocal IOLs are effective at improving near vision relative to monofocal IOLs. Whether that improvement outweighs the adverse effects of multifocal IOLs will vary between patients. Motivation to achieve spectacle independence is likely to be the deciding factor.


T A B L E O F C O N T E N
To address this problem, new lenses have been developed that provide two or more points of focus. These are known as 'multifocal' lenses. These are designed to reduce the need for spectacles. People with multifocal lenses may have more vision problems such as glare and seeing haloes. Another option is to put a different monofocal lens in each eye: one with a focus for near vision and one with a focus for distance vision. This is known as 'monovision'.
What are the main results of the review?
The Cochrane researchers found 20 relevant studies that were mainly conducted in Europe and North America (15 studies); three studies were conducted in China and one study each in the Middle East and India. Eighteen studies compared multifocal with monofocal lenses and two studies compared multifocal lenses with monovision.
The Cochrane researchers assessed how certain the evidence is for each review finding. They looked for factors that can make the evidence less certain, such as problems with the way the studies were done, very small studies, and inconsistent findings across studies. They also looked for factors that can make the evidence more certain, including very large effects. They graded each finding as very low, low, moderate or high certainty The review shows that: • People with multifocal lenses probably have distance vision that is not very different to the distance vision of people who have standard monofocal lenses after cataract extraction (moderate-certainty evidence). However, people with multifocal lenses may have better near vision and may be less likely to need spectacles compared with people with monofocal lenses (low-certainty evidence).
• People who have multifocal lenses may be more likely to experience haloes and glare compared with people who have monofocal lenses (low-certainty evidence).
• People receiving multifocal lenses had similar distance vision and near vision compared with people receiving monovision but reported less spectacle dependence. People with multifocal lenses reported more problems with glare and haloes compared with people with monovision.

How up-to-date is this review?
The Cochrane researchers searched for studies that had been published up to 13 June 2016. On average m ost people in both groups achieved high scores on VF-7/ VF-14 questionnaires but inconsistent com parative results between the 2 groups

Description of the condition
Cataract, defined as the presence of visually impairing lens opacity in one or both eyes, is present in 30% of people aged 65 years and over in the UK (Desai 1999). Around 400,000 cataract extractions were performed in England in the year 2014 to 2015 (Department of Health 2015). People with cataract usually present with one or more of the following symptoms: gradual reduction in visual acuity (VA), glare, change in glasses prescription and change in colour appreciation. The diagnosis may be made by the person's general practitioner or optometrist followed by referral to an ophthalmic surgeon for confirmation of the diagnosis and management. Many people with treatable visual impairment from cataract do not access health services (Desai 1999).

Description of the intervention
Cataracts causing only mild symptoms may not need treatment, while changes in glasses prescription due to cataract may simply be managed by the provision of new glasses. Where these options are inadequate the only treatment available is surgical extraction of the cataract. This is routinely accompanied by implantation of an intraocular lens (IOL) to replace the focusing power of the natural lens. Current techniques of cataract surgery and IOL implantation allow accurate prediction of postoperative refraction. Existing standards of best-corrected postoperative VA (Desai 1993) are being replaced by an expectation of good uncorrected distance acuity. This has been driven partly by the change from cataract surgery using a large (10 mm) incision to small incision (2 mm to 4 mm) phacoemulsification surgery. This change is generally perceived to offer greater predictability of refractive outcomes, a necessary pre-requisite for good VA without the need for glasses. Cochrane systematic reviews comparing surgical approaches have been published (Ang 2012;Riaz 2013;de Silva 2014). Because standard IOLs have a fixed refractive power the focal length is also fixed (monofocal). This means that most people will require a reading addition to their distance glasses prescription (Javitt 1997). While most people undergoing cataract surgery may be happy to use reading glasses, a proportion are likely to seek good unaided near vision as well as distance vision. The need for reading glasses for near vision is unlikely to be considered an important issue at present in low-income countries where the burden of blindness due to cataract is so high.

How the intervention might work
One approach to improve near VA is to modify the IOL. There are no IOLs currently available that can change shape during accommodation in the manner of the natural crystalline lens. A fixed-shape optic IOL could theoretically provide near vision if attempted accommodation resulted in forward displacement of the IOL. Efforts to design an IOL using this principle have so far been unsuccessful (Legeais 1999). An IOL can also provide near and distance vision if both powers are present within the optical zone. This has been attempted using diffractive optics or with zones of differing refractive power. Both types of IOL divide light up to focus at two (bifocal) or more (multifocal) points so that the person can focus on objects at more than one distance from them. IOLs of both types are currently commercially available. Optical evaluation of multifocal IOLs has been performed in detail. Exact figures vary with the IOL tested but essentially a twoto three-fold increase in the depth of field is achieved at the expense of a 50% reduction in the contrast of the retinal image (Holladay 1990;Lang 1993). Clinical evaluation of a multifocal IOL is less clear-cut. Several large studies, including non-randomised comparisons with monofocal IOLs, have indicated that the quality of vision with bifocal and multifocal IOLs is good (Gimbel 1991;Knorz 1993;Lindstrom 1993;Steinert 1999). The key question to be answered is whether the optical trade-off inherent in a multifocal IOL results in better or worse visual function compared to a monofocal IOL. Objective (Desai 1993) and subjective (Desai 1996) improvement in vision following cataract surgery with monofocal IOL implantation is so high that any study lacking a randomised control group as a comparator will be relatively uninformative.

Why it is important to do this review
There is an extensive body of published data on both monofocal and multifocal IOLs describing largely successful outcomes. To draw some conclusions regarding the relative merits of the different IOL types we undertook a systematic review of the best quality data (that from randomised controlled trials).

O B J E C T I V E S
To assess the visual effects of multifocal IOLs in comparison with the current standard treatment of monofocal lens implantation.

Types of studies
We included randomised controlled trials.

Types of participants
We included trials in which participants were undergoing cataract surgery and IOL implantation in one or both eyes. There were no restrictions on race, gender or ocular comorbidity. We excluded trials that included participants with paediatric cataract (onset prior to age 16 years).

Types of interventions
We included trials in which any type of diffractive or refractive multifocal IOL was compared with monofocal IOL implantation.
In the current update 2016 we considered two comparisons. This was a protocol amendment (see Differences between protocol and review for further explanation).

Types of outcome measures
Outcome data were collected at the longest time postoperatively that was available in each study. We revised the outcomes for the update in 2016 (see Differences between protocol and review).

Primary outcomes
• Distance, intermediate and near VA (unaided and corrected).
• We used the cut-point of worse than 6/6 for distance VA (20/20, logMAR score > 0) as 6/6 vision is usually considered normal VA. We used the cut-point of worse than J3/J4 (Jaegar cards) or equivalent for near VA.
• We also considered VA as a continuous variable where it was reported in logMAR units.
• Spectacle dependence as reported by the participant.

Secondary outcomes
• Contrast sensitivity (contrast is the difference between the brightness of an image and its background divided by the total brightness of image plus background. Contrast sensitivity is the inverse of target contrast threshold).
• Participant-reported outcomes including: • quality of life or visual function as measured by validated instruments; • informal (non-validated) subjective assessment of visual function; • participant satisfaction; • glare (glare occurs when a light source other than the target image illuminates the retina, resulting in reduced contrast. Scatter of light from the glare source by the optics of an IOL may cause unequal glare between participants); • other optical aberrations including halos. • Resource use and costs.

Adverse effects
• Any other adverse effects or complications as reported in trial reports.  Clinical-Trials.gov (www.clinicaltrials.gov), and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 13 June 2016. See: Appendices for details of search strategies for CENTRAL (Appendix 1), MEDLINE (Appendix 2), Embase (Appendix 3), ISRCTN (Appendix 4), ClinicalTrials.gov (Appendix 5) and the ICTRP (Appendix 6).

Searching other resources
We searched the reference lists of relevant articles and Martin Leyland's personal database of trials. For the first version of the review we contacted investigators of included studies and the manufacturers of multifocal IOL (Acute Care; Spectrum Ophthalmics; Storz Ophthalmics; Bausch & Lomb Surgical Ltd (UK); Alcon Laboratories Ltd; Pharmacia & Upjohn; Rayner Intraocular Lenses Ltd) for details of additional published and unpublished trials. We did not do this for subsequent updates.

Selection of studies
Two review authors working independently examined the titles and abstracts from the electronic searches. We obtained the full paper of any trial that appeared to fit the inclusion criteria. We assessed full copies according to the definitions in the Criteria for considering studies for this review. We only assessed trials meeting these criteria for risk of bias.

Data extraction and management
For the update 2016, partly because we had revised the outcomes but also because we needed to incorporate more information as a result of the updated methodological expectations of Cochrane Reviews (MECIR 2013), we extracted the data for all trials again using a piloted customised data extraction template in web-based review management software (Covidence 2016). Review author pairs extracted data independently (JE/VK/MZ) and a third review author (SdeS) adjudicated discrepancies as needed. We imported data directly from Covidence into Review Manager 5 (RevMan 2014), which was checked by one review author (JE).

Assessment of risk of bias in included studies
Review author pairs (JE/VK/MZ) independently assessed risk of bias in Covidence using Cochrane's tool for assessing risk of bias (Higgins 2011) and as outlined in Table 1.

Measures of treatment effect
Our measure of treatment effect was the risk ratio (RR) for dichotomous outcomes and mean difference (MD) or standardised mean difference (SMD) for continuous outcomes, with 95% confidence intervals (CI). The use of the MD was a protocol amendment -see Differences between protocol and review. Where possible, we checked for skewness using the method outlined in the Cochrane Handbook for Systematic Reviews of Interventions (Deeks 2011).

Unit of analysis issues
The intervention could be applied to one or both eyes. We have indicated for each trial whether unilateral or bilateral surgery was done. For the unilateral trials, the outcome was measured on the operated eye. For the bilateral trials, the outcome could be measured and reported on both eyes, or for the person (i.e. binocular vision). Where available, we have chosen reported binocular vision for the analyses. Where data were reported for both eyes, and appropriate methods of adjustment were not included, we requested further data from the investigators. For studies with multiple multifocal treatment groups, we combined data for the different groups using the Review Manager 5 calculator (RevMan 2014).

Dealing with missing data
The analyses in this review were available case analyses. This makes the assumption that data were missing at random. We recorded the amount of missing data and reasons for exclusions and attrition, where available and documented this in the 'Risk of bias' table for each study (Characteristics of included studies table, "incomplete outcome data").

Assessment of heterogeneity
We assessed heterogeneity by examining the forest plots to see whether the direction of effect was similar in all studies and whether the CIs for the individual study estimates overlapped. To assess the role of chance we used the Chi 2 test, although this may have low power when there are few studies, or the studies are small. We also considered the I 2 statistic (Higgins 2003). We took an I 2 value of 50% or more to indicate substantial inconsistency in study results.

Assessment of reporting biases
We assessed publication bias when the meta-analysis included 10 or more trials by plotting effect size against standard error.

Data synthesis
Where three or more studies contributed to the analyses, we pooled the data using a random-effects model. If there were fewer than three studies, we used a fixed-effect model. If there was substantial heterogeneity or inconsistency (see Assessment of heterogeneity), we did not report the pooled analyses unless all individual study estimates were in the same direction.

Subgroup analysis and investigation of heterogeneity
We considered two main sources of heterogeneity: type of lens (refractive or diffractive) and whether the surgery was unilateral or bilateral. We compared subgroups using the standard test for interaction implemented in Review Manager 5 (RevMan 2014).

Sensitivity analysis
We performed a sensitivity analysis excluding studies at high risk of bias in one or more domains. This was a protocol amendment (see Differences between protocol and review).

'Summary of findings' table
We prepared a 'Summary of findings' table presenting absolute and RRs with an assessment of the overall quality of the evidence using GRADE (GRADEpro 2014). We included the following outcomes in the table.
• Participant-reported outcomes: quality of life or visual function.

Original review
The initial electronic searches found 239 titles and abstracts. We obtained the full copies of possibly relevant papers according to the criteria specified (see Search methods for identification of studies). One trial did not include a monofocal control group and was excluded (Walkow 1997). We identified nine papers as meeting the inclusion criteria for this review. On contacting the authors, we identified three as descriptions of the same cohort of participants (Haaskjold 1998a). Interim data were available on 149 participants with five to six months' follow-up (Allen 1996), and a subsequent paper reported corrected distance acuity and contrast sensitivity data only (with no numerical data for contrast sensitivity) on 221 participants (Haaskjold 1998b). An unpublished report from the lens manufacturer described limited data on 190 participants at one year (Pharmacia 1995). The study author was also able to supply additional unpublished results. . We checked the status of the ongoing studies published in the previous version of this review and have excluded one study (NCT01088282) and study ISRCTN37400841 has been completed and included (Wilkins 2013). We re-assessed one study which was previously included and have now excluded the study (Alio 2011c).

Included studies
Details of the individual trials are summarised in Table 2; information on the individual trials are included in the Characteristics of included studies table.

Design
There were four multicentre and 16 single-centre studies.

Participants
The total number of people enrolled was 2230. Of these people, 2061 (3194 eyes) were followed up and were included in the analyses. The smallest study randomised 40 people (Kamlesh 2001) and the largest trial randomised 261 people (Javitt 2000). All studies recruited people with age-related cataract with no other apparent ocular morbidity and without excess corneal astigmatism. Table 3 shows the mean age and sex of people enrolled in these trials. The median mean age was 69 years and median percentage women was 57%.

Interventions
The studies considered different types of multifocal lenses including refractive (10 studies), diffractive (six studies), mixture of refractive and diffractive lenses (three studies) and one study used a multifocal lens with both refractive and diffractive properties (Table 4). Two studies compared the multifocal lens to monovision (Wilkins 2013; Labiris 2015). The cataract surgery performed in 16 studies was small incision phacoemulsification. Three studies employed extracapsular cataract extraction and one study included both types of surgery.
In 12 studies the cataract surgery was bilateral in all or some people (participants had the same type of lens inserted into both eyes). In cataract surgery, the lens capsule must be breached to gain access to the crystalline lens. A continuous circular tear (capsulorhexis) is preferred to the older 'can-opener' technique using multiple small tears or incisions because the incidence of postoperative IOL decentration is likely to be reduced. Decentration leads to induced astigmatism and a reduction in unaided VA. Most studies used capsulorhexis and four studies used envelope capsulotomy (el Maghraby 1992;Percival 1993;Rossetti 1994;Kamlesh 2001 2008). Even trials using the same chart did not report the results in the same way -the data were described variously as contrast sensitivity, VA at different contrast levels and difference between high contrast and lower contrast acuity -and it was difficult to pool data for contrast sensitivity. Three studies assessed the extent of glare disability using the Brightness Acuity Tester (Steinert 1992;Leyland 2002;Harman 2008), and most studies elicited information from participants as to the extent of problems with glare or haloes (or both). Some studies formally addressed visual functioning after surgery using validated instruments such as the VF-

Excluded studies
See Characteristics of excluded studies table.

Risk of bias in included studies
See Figure 2 and Figure 3.  We contacted the authors of included papers for further information on their studies. We received replies clarifying various methodological issues for three studies (el Maghraby 1992;Haaskjold 1998a;Javitt 2000).

Allocation
Eight studies described an adequate method for random sequence generation ( . The other studies did not report any information on how the sequence was generated but were described as "randomised". Seven studies provided a convincing description of allocation concealment (

Masking (performance bias and detection bias)
Four studies described masking of participants (Steinert 1992; Javitt 2000; Cillino 2008; Wilkins 2013). In Harman 2008, the IOL type was disclosed to participants at the three-month visit. All outcomes for this study have therefore been reported for the three-month visit prior to the IOL disclosure, except for spectacle dependence and symptoms of glare/haloes that were only reported at the 18-month visit. Interestingly, following disclosure of multifocal IOL status, participants in this group showed an improvement in near vision and spectacle independence by the 18-month visit. Several studies mentioned masking but it was not clear how successful it had been. In Leyland 2002, participants were informed that the IOL type implanted would not be revealed to them until completion of the trial but a proportion of participants were reported to be unmasked; in Palmer 2008, participants were not told which lens they would receive but it was unclear whether any of them could have guessed; in Peng 2012, the study was described as a "prospective, randomised, comparative, and observer-masked trial" but there was no information on masking in the study report; in Zhao 2010, participants and medical staff collecting data were masked but there was no information on the staff providing care. The remaining studies did not mention masking and we have assumed therefore that it was not done. Labiris 2015 did not describe masking and on the clinical trials registry was described as 'open label'. Three studies that were (possibly) not masked successfully to participants reported masking outcome assessors (Leyland 2002;Harman 2008;Zhao 2010). In general, studies that masked participants and personnel also masked outcome assessors, the exception being Wilkins 2013.

Incomplete outcome data
We judged attrition bias to be low risk in two studies where reasons and numbers of participants who exited the study after intervention and before outcomes were clearly reported and we thought unlikely to affect the outcome (Peng 2012; Wilkins 2013). Five studies were at high risk of attrition bias (Steinert 1992;el Maghraby 1992;Percival 1993;Nijkamp 2004;Sen 2004). This was either due to significant numbers of participants being lost to followup without clear indication of which group they had been randomised to, or exclusion of participants after randomisation based on outcome such as high astigmatism. However, most studies did not clearly report follow-up and it was difficult to make a judgement.

Selective reporting
The extent to which selective reporting had occurred for each individual study was unclear because in general we did not have access to study protocols. Of studies registered prospectively on a publicly available database, Labiris 2015 was deemed to have low reporting bias since all outcomes were reported; for Wilkins 2013, there were some differences between the trial registry entry and outcomes reported.

Effects of interventions
See: Summary of findings for the main comparison Multifocal compared to monofocal intraocular lenses after cataract extraction The lenses used in each study are detailed in Table 4 and refractive aims are summarised in Table 5. Five studies compared two (el Maghraby 1992; Leyland 2002), three (Cillino 2008; Palmer 2008), or four (Rasp 2012) different multifocal IOLs with a monofocal control group. The multifocal IOL results within these studies were similar and therefore we have pooled them for this review.

Distance visual acuity
Eight studies reported the number of participants who did not achieve an unaided VA of 6/6 (n = 682) (Analysis 1.1). These tended to be older studies (Steinert 1992;el Maghraby 1992;Percival 1993;Rossetti 1994;Haaskjold 1998a;Leyland 2002;Sen 2004;Jusufovic 2011). There was little evidence for any important difference between the two groups with a pooled risk ratio (RR) 0.96, 95% confidence interval (CI) 0.89 to 1.03). We judged this to be moderate-certainty evidence, downgrading one level for risk of bias (Summary of findings for the main comparison). Six studies reported mean unaided logMAR VA (n = 848) (Analysis 1.2). There was substantial inconsistency (I 2 = 74%) but in all studies the mean difference between groups was less than 0.1 logMAR.
Eight studies reported the number of participants that did not achieve a corrected VA of 6/6 (n = 692) (Analysis 1.3). Again these studies were older, all being conducted no later than 2004. There was inconsistency (i 2 =54%) possibly reflecting changes over time in lenses used. The individual study estimates ranged from RR 0.20 (95% CI 0.03 to 1.56) (Kamlesh 2001) in favour of multifocal lenses to 1.50 (0.63 to 3.59) (Percival 1993) in favour of monofocal lenses. We judged this to be very low-certainty evidence, downgrading one level for risk of bias, one level for imprecision due to the wide CIs and one level for inconsistency. (Summary of findings for the main comparison). Six studies reported mean corrected logMAR VA (n = 848) (Analysis 1.4). There was no evidence for any major difference between groups with all studies reporting a mean difference of 0.1 logMAR or less but again with substantial inconsistency (I 2 = 64%).

Near visual acuity
Eight studies reported unaided near VA of worse than J3/J4 or equivalent (n = 782) (Analysis 1.6). There was significant heterogeneity in the method used for near VA measurement which may affect the accuracy of pooled outcomes. People receiving a multifocal lens were less likely to have poor near vision (RR 0.20, 95% CI 0.07 to 0.58). We judged the evidence to be of low-certainty. We downgraded one level for risk of bias and one level for inconsistency between studies (I 2 = 93%). The RRs ranged from 0.02 (Jusufovic 2011) to 0.73 (Leyland 2002) in the individual studies (Summary of findings for the main comparison). Five studies reported mean unaided near VA (n = 829) (Analysis 1.7). There was substantial inconsistency between studies (I 2 = 98%) but all studies favoured the multifocal group. Four studies reported corrected near VA worse than J3/J4 or equivalent (n = 344) (Analysis 1.8). There were better outcomes in the multifocal group (RR 0.32, 95% CI 0.08 to 1.27, I 2 = 18%). Six studies reported mean corrected near VA (n = 1003) (Analysis 1.9). There was substantial inconsistency (I 2 =99%). Four studies reported similar VA in both groups with a mean difference of less than or equal to 0.

Spectacle dependence
Ten studies (n = 1000) reported the outcome of spectacle dependence for distance or near vision (Analysis 1.11). Fewer participants in the multifocal group were spectacle dependent in the multifocal compared with the monofocal group (RR 0.63, 95% CI 0.55 to 0.73). There was substantial heterogeneity between studies (I 2 = 67%) but all studies favoured multifocal IOLs. Since there were data from 10 studies for this outcome, we produced a funnel plot to evaluate publication bias as planned in our protocol. This showed evidence of publication bias with a skewed pattern ( Figure  4). We downgraded the evidence for spectacle independence one level for risk of bias and one level for publication bias. We did not additionally downgrade for inconsistency (Summary of findings for the main comparison). Four studies reported spectacle dependence for distance vision (n = 618) which overall was reduced in the multifocal group (RR 0.71, 95% CI 0.46 to 1.09) (Analysis 1.11). However, there was some inconsistency between studies with two studies showing no overall difference and with the other two studies in favour of the multifocal group (I 2 = 67%). Six studies reported spectacle dependence for near vision (n = 772) (Analysis 1.11). Fewer participants in the multifocal group required spectacles for near vision (RR 0.53, 95% CI 0.40 to 0.71). Again there was wide variation between studies (I 2 = 85%) but all had better outcomes in the multifocal group.

Contrast sensitivity
Thirteen studies measured contrast sensitivity; however, they used several different methods (see 'Outcomes' of Included studies) and therefore combined analysis of results was difficult. We pooled and analysed data from four trials (n = 288) that used the Pelli-Robson chart (Analysis 1.12). This indicated little evidence of any important difference in contrast sensitivity between groups (MD -0.09, 95% CI -0.26 to 0.08).
The remaining studies reported poorer contrast sensitivity outcomes in the multifocal group. One study reported a small difference in contrast sensitivity in participants with good VA (Haaskjold 1998a); three studies reported contrast sensitivity at a particular spatial frequency (Cillino 2008;Palmer 2008;Zhao 2010), and four studies reported overall poorer contrast sensitivity in the multifocal group (Steinert 1992;Percival 1993;Kamlesh 2001;Ji 2013).

Participant-reported outcomes: visual function and quality of life
Four studies reported results of visual function questionnaires (n = 480) (Analysis 1.13). There was some evidence of more favourable outcomes in the multifocal group, however the size of the effect was small and uncertain due to wide CIs and there was inconsistency between studies such that a pooled result may not be meaningful.
Only one study assessed vision-related quality of life and found no difference between multifocal or monofocal IOL groups (Analysis 1.14).

Participant-reported outcomes: satisfaction
Six studies reported satisfaction scores (n = 643). The difference between groups was uncertain due to inconsistency between studies (I 2 = 88%) (Analysis 1.15). Four studies reported the number of participants that reported having 'good' vision or being 'satisfied' with their overall vision (n = 388). There was no evidence of any important differences between groups (RR 0.99, 95% CI 0.92 to 1.06) (Analysis 1.16).
One study assessed participant satisfaction for near vision (n = 80) and found a greater number of participants reporting good outcomes in the multifocal IOL group (RR 1.42, 95% CI 1.13 to 1.78) (Analysis 1.16) (Rossetti 1994). The same study also assessed participant satisfaction for distance vision with a slightly greater level of satisfaction in the monofocal group (RR 0.89, 95% CI 0.72 to 1.10) (Analysis 1.16).
One study assessed visual satisfaction at 12 months using the TyPE questionnaire and found no difference between groups (Analysis 1.17) (Leyland 2002).

Cataract symptom scores
Two studies with 257 participants reported cataract symptom scores (Analysis 1.18). Both studies used the Cataract Symptom Score (CSS) (Steinberg 1994). Nijkamp 2004 reported final value at 3 months, Sen 2004 reported change between surgery and 1 month.
The CSS requires participants to reported whether they are bothered by any of five symptoms: double or distorted vision; seeing glare, halo, or rings around light; blurry vision; colours looking different than they used to in a way that is disturbing; and worsening of vision within the past month. A score was given for each symptom: 0 = "no symptom or not bothered"; 1="a little bothered"; 2 = "somewhat bothered"; and 3 = "very bothered". A total score of 15 was possible ranging from 0 (no symptoms or not bothered by any of the symptoms) to 15 (very bothered by all five symptoms). On average people in the multifocal group had worse symptom scores (MD 1.01 score, 95% CI 0.39 to 1.64; I 2 = 0%).

Glare
Seven studies (n = 544) assessed postoperative glare. More people in the multifocal group reported problems with glare: (RR 1.41, 95% CI 1.03 to 1.93) (Analysis 1.19). We judged this to be lowcertainty evidence downgrading one level for risk of bias and one level for imprecision as the lower CI was close to 1 (Summary of findings for the main comparison).

Haloes
Seven studies (n = 662) questioned participants regarding postoperative haloes. More people in the multifocal group reported haloes (RR 3.58, 95% CI 1.99 to 6.46) (Analysis 1.20). We judged this to be moderate-certainty evidence downgrading one level for risk of bias (Summary of findings for the main comparison).

Complications
Complications of surgery can be expected to be similar for multifocal and monofocal IOLs as the lenses are similar in all but the design of the optics and require no modifications to surgical technique. Ten studies reported perioperative and postoperative complications (el Maghraby 1992;Percival 1993;Javitt 2000;Leyland 2002;Sen 2004;Nijkamp 2004;Cillino 2008;Harman 2008;Zhao 2010;Peng 2012). The incidence of complications was low and similar in the multifocal and monofocal groups.

Subgroup analyses
We did two subgroup analyses: refractive lenses versus diffractive lenses (Table 6) and bilateral surgery versus unilateral surgery (  Table 7). These analyses must be interpreted with caution due to the small numbers of studies in each group which means the test for interaction may have low power and the large number of outcomes which may lead to spurious findings. Comparing diffractive and refractive lenses, there was some indication that the diffractive lenses performed better. Specifically diffractive lenses had better visual function questionnaire scores and better satisfaction scores, and lower spectacle dependence. The comparison between bilateral and unilateral surgery was difficult to interpret. There were two outcomes that had a significant P value for interaction, corrected distance VA worse than 6/6 and visual function scores, but in both these cases there was only one trial in some of the subgroups so it is difficult to attribute the difference in effect solely to this characteristic.

Sensitivity analysis
We excluded studies at high risk of bias in one or more domain as planned in our protocol (Table 8). There were some differences in outcome but these were not consistent and, due to the relatively high proportion of trials at high risk of bias, it is difficult to interpret these comparisons due to increased imprecision.

Multifocal lenses versus monovision
Two studies compared multifocal lenses with monovision (Wilkins 2013; Labiris 2015). In Wilkins 2013, the investigators enrolled 212 people who received bilateral sequential cataract surgery either to receive bilateral Tecnis ZM900 diffractive multifocal lenses or Akreos AO monofocal lenses with the powers adjusted to target -1.25 D monovision. The participants were followed up to four months and 187 (88%) were seen at that point. In Labiris 2015, the investigators enrolled 75 people who received bilateral cataract surgery either to receive bilateral Isert PY60MV refractive multifocal lenses or SN60WF monofocal lenses with the powers adjusted to target -1.25 D monovision. The participants were followed up to six months. Follow-up was unclearly reported but the impression was given that all 75 participants were followed up.
There was no evidence for any important difference in distance VA between the two groups (MD 0.

Summary of main results
The results are summarised in Summary of findings for the main comparison. Distance VA was similar in the multifocal and monofocal groups but people with multifocal lenses achieved better near vision overall and were less dependent on spectacles. Adverse subjective visual phenomena, particularly haloes, were common and troublesome in people receiving multifocal IOLs.
There was some evidence that contrast sensitivity may be lower in people receiving multifocal IOLs. The differences were smaller than would be expected given the division of light between distance and near focus, which may result from visual processing. Whether the reduction in contrast sensitivity induced by the IOL would be clinically significant would depend on the contrast presented by the visual target and the contrast sensitivity of the person's retina. There were no significant differences between IOLs with respect to objective glare. Participant satisfaction was not consistently reported between the two lens types. There was some evidence that participants with multifocal lenses experienced improved visual functioning for tasks requiring near vision compared to participants with monofocal lenses. There was less evidence available for the comparison between multifocal lenses and monovision. The data available suggested similar distance and better near VA in the multifocal and monovision groups. Multifocal lenses were associated with less spectacle dependence but also an increased chance of experiencing glare and haloes compared with monovision.

Overall completeness and applicability of evidence
Ten of the 20 included studies involved participants with surgery on both eyes and two studies had a mixture of both unilateral and bilateral surgery. Unilateral studies allow measurement of uniocular outcomes such as VA but are of limited use when attempting to measure the effect of the multifocal IOLs on quality of life, especially where the fellow eye has good vision. Of the studies that involved unilateral surgery only, Steinert 1992 and Rossetti 1994 reported fellow eye vision as good, Percival 1993 described the fellow eyes as cataractous and Jusufovic 2011 and Zhao 2010 commented that participants had no prior ocular surgery suggesting a phakic status in the other eye. The other studies involving unilateral surgery and the two studies that performed surgery on one or both eyes did not comment on the status of the fellow eye.
We presented results as a combined group of refractive and diffractive IOL studies. Combination of data was valid as both IOL types use the same principle of simultaneous vision once incident light has been split by either the refractive or diffractive optic. Holladay 1990 found very similar optical properties of all multifocal IOLs tested including the Array refractive IOLs and the 3M diffractive IOL used in some of the studies reviewed here (the Pharmacia diffractive IOL is of a similar design to the 3M IOL). We presented separated data, which are likely to become more useful as further studies are published. Unaided near vision is critical to assessment of multifocal efficacy but was reported in a manner that made comparison between studies difficult. Only eight studies reported unaided near VA worse than J3/J4 or equivalent, and five studies reported mean LogMAR unaided near VA allowing pooled data analysis. Furthermore, only seven studies reported both unaided and corrected near acuity and Palmer 2008 reported corrected near acuity together with unaided near acuity but wearing a distance correction. Reading distances differed in the individual studies and it was unclear in most studies whether the reported print size read had been corrected for reading distance to allow a near acuity to be calculated. A further problem arose because Jaeger cards are not standardised between manufacturers so that J3 from one study cannot be assumed to equal J3 from another (Bailey 1978). Despite these caveats, it is likely that unaided near vision is improved by a multifocal IOL. It is important to remember, however, that monofocal IOL near acuity can be restored using reading glasses. This review has highlighted the need for a core set of outcome measures in trials comparing multifocal and monofocal lenses. Ideally these outcomes should be based on validated measures, particularly for the more subjective outcome measures. The optical and visual effects of these IOLs are now well-known, particularly near vision. The search for alternative strategies to achieve spectacle independence, such as monovision and accommodating IOLs, should continue.

Quality of the evidence
We graded the certainty of the evidence as low to moderate for those outcomes for which we could estimate an effect (Summary of findings for the main comparison). In general, we downgraded results for risk of bias because it was difficult to mask participants and outcome assessors in these trials and difficult to assess reporting bias. There was substantial methodological and statistical heterogeneity for some outcomes, in particular for the measurement of corrected distance VA and both unaided and corrected near VA, as well as participant-reported spectacle dependence. There was also some evidence of publication bias with respect to the outcome of spectacle dependence.

Agreements and disagreements with other studies or reviews
One meta-analysis of outcomes of multifocal IOLs that included both randomised controlled trials and studies of other design found slightly better uncorrected distance VA in the monofocal groups but better uncorrected near VA and greater spectacle independence in the multifocal group, the latter being similar to the results from our analysis (Cochener 2011). They also reported better near VA using diffractive (rather than refractive) multifocal IOLs, which is similar to the outcomes we found albeit with small numbers used for analysis. de Vries and colleagues conducted a review including both randomised controlled trials and case series (de Vries 2013). This was a narrative review summarising the outcomes of included studies but did not draw any definitive conclusions regarding outcomes that could be compared with results presented in this systematic Cochrane Review.

Implications for practice
Multifocal intraocular lenses may result in better near vision without any adverse effect on distance acuity. Spectacle dependence is less likely with use of these intraocular lenses when compared to the standard practice of monofocal implantation.
Whether the improvement in unaided near vision and increased incidence of spectacle independence are sufficient to outweigh the experience of glare and haloes is a matter for each person to decide. The final choice is likely to depend on a person's motivation to be free of spectacles, guided by realistic expectations as to the likelihood of achieving this aim and understanding of the compromises involved.

Implications for research
This review has highlighted the need for a core set of outcome measures in trials comparing multifocal and monofocal lenses. Standardised outcome reporting for visual acuity is required to be able to pool data and draw robust conclusions. Ideally these outcomes should be based on validated measures, particularly for the more subjective outcomes, and include the views of people who have had cataract surgery.
The search for alternative strategies to achieve spectacle independence, such as monovision, trifocal and accommodating intraocular lenses, should continue.
This work was undertaken in collaboration with the National Institute for Health and Care Excellence (NICE). The views expressed in this publication are those of the authors and not necessarily those of NICE.
We would like to thank: • David Calladine, Edward Pringle, Sweata Shah and Eduardo Zinicola (EZ) for co-authoring previous versions of this review; • Anupa Shah, Managing Editor for Cochrane Eyes and Vision (CEV), for her help throughout the review process, • the CEV editorial team for creating and running the electronic search strategies; • the study authors and pharmaceutical companies who kindly responded to queries during data collection; • Mr Bruce Allan MD FRCOphth for comments on the protocol and review drafts; • Mr Oliver Findl and Dr Alicja Rudnicka for their comments on the review update; • Taixiang Wu for contacting Chinese-speaking trialists for information about trials (Xu 2007; Huang 2010; Ji 2011).

Cillino 2008
Methods Allocation concealment Low risk Quote: "The randomization code was maintained only at the central data facility and was not broken until all data analysis was complete." Blinding of participants and personnel All outcomes Low risk Quote: "The patients and the medical staff who collected functional data and qualityof-life data were masked to the type of lens that each patient received." Judgement comment: not possible to mask the operating surgeon but we judged that this would not have important effect on risk of bias Blinding of outcome assessors All outcomes Low risk Quote: "The patients and the medical staff who collected functional data and qualityof-life data were masked to the type of lens that each patient received." Judgement comment: outcome assessors were masked.
Incomplete outcome data All outcomes Unclear risk Quote: "Four patients withdrew after randomization or during the postoperative period. Two patients were excluded from the analysis because of the presence of capsular brosis at 1 week postoperatively." Judgement comment: 91% of participants followed up but some exclusions after randomisation and unclear which group these were in There was a third treatment group in this study that was not included in this review (accommodative lenses, 1CU) Quote: "Patients who had >1 D (and <2 D) of corneal astigmatism also underwent limbus-relaxing incisions (LRIs), using the modified Gills nomogram (21) at the time of surgery, aiming for postoperative astigmatism of <1 D." Quote: "Ten patients required LRIs at the time of surgery: 5 from the 1CU group [not included in this review], 3 from the multifocal, and 2 from the monofocal. Of these, only 1 patient from the multifocal group required bilateral LRIs."

Outcomes
Note: participants were asked to practice reading every day without spectacle correction until 3

Bias Authors' judgement Support for judgement
Sequence generation Low risk Quote: "A block randomization schedule by patient was prepared for each site using SAS software, (SAS Institute, Cary, NC)." Allocation concealment Unclear risk Quote: "Assigned in blocks of two. For each block of two patients, either the rst patient or the second (in random order) received a multifocal lens. The randomization schedule." Quote: "The randomization schedule was drawn up by site before the start of the study, and the assignment of each patient was placed in a sealed container that was not opened until the patient was actually in the operating room. Differences between the ultimate size of the monofocal and multifocal groups resulted from patients withdrawing from study after just one implant, sites stopping ahead of schedule, and chance outcomes." Judgement comment: although efforts make to conceal the allocation a block size of 2 may have been very easy to second guess Blinding of participants and personnel All outcomes Low risk Quote: "The patients, the ophthalmic technicians who collected clinical data, and the interviewers who collected the quality-oflife data were all masked as to the type of lens that each patient received." Blinding of outcome assessors All outcomes Low risk Quote: "The patients, the ophthalmic technicians who collected clinical data, and the interviewers who collected the quality-oflife data were all masked as to the type of lens that each patient received."

Javitt 2000 (Continued)
Incomplete outcome data All outcomes and Herzegovina

Bias Authors' judgement Support for judgement
Sequence generation Low risk Quote: "Included 50 patients with implanted monofocal IOLs. Randomization was performed as follows: 100 small folded pieces of paper on which "multi" or "mono" was written, are folded and placed in an opaque bag." Allocation concealment Low risk Quote: "The nurse who did not participate in the study picked papers from the bag and divided patients into two groups. Also, surgeon who carried out the operations did not know which group does the patient belong, until the very moment of intraocular lens implantation." Blinding of participants and personnel All outcomes • Ethnic group: NR Inclusion criteria: bilateral senile cataract; astigmatism < 1.5 D; spectacle sphere -6.0 to +4.0 D; axial length 19.5 mm to 26 mm; ability to complete questionnaires in Dutch Exclusion criteria: professional night driver; mental retardation (diagnosed in the medical file or concluded by contact by telephone); any eye disease other than cataract that might limit postoperative vision Pretreatment: slightly more astigmatism in the monofocal group

Bias Authors' judgement Support for judgement
Sequence generation Low risk Quote: "Block randomization by means of a computerized random number generator was used to keep the number of subjects in the different groups balanced." Allocation concealment Low risk Quote: "After the preoperative assessments, a technical ophthalmic assistant allocated the treatment condition via a sealed envelope that contained a card identifying the lens type. The envelope was opened by a nurse not involved in the study. This was done after biometry and just before surgery, to enable the ophthalmologist to choose the correct lens power." Blinding of participants and personnel All outcomes High risk Quote: "Patients were masked with respect to the type of lens until the first postoperative visit. It was unfeasible to keep patients masked postoperatively, because they were aware of the characteristics of both types of IOL from their description in the patient information they received." Quote: "Interviewers and ophthalmologists were unaware of the treatment group of the patient at the preoperative tests. However, because there were perceptible differences between the 2 types of lenses during the slit-lamp examination, masking of interviewers and ophthalmologists was not feasible postoperatively." Blinding of outcome assessors All outcomes High risk Quote: "Interviewers and ophthalmologists were unaware of the treatment group of the patient at the preoperative tests. However, because there were perceptible differences between the 2 types of lenses during the slit-lamp examination, masking of interviewers and ophthalmologists was not feasible postoperatively." Incomplete outcome data All outcomes High risk Judgement comment: rather high loss to follow-up (approximately 30%) potentially linked to outcome although similar loss to follow-up in both groups. Excluded people with high astigmatism after surgery Quote: "Patients with a postoperative refractive error in spherical equivalent (SE) of >1.5 D from emmetropia (in at least one eye) were excluded from further analyses (Fig 1; monofocal

Savage, November 2004 Summary
The conclusions of the review abstract suggest that multifocals [intraocular lenses (IOL)] improved quality of near vision over the monofocal IOL, however in several studies noted (ie: Javitt & Steinert) the refractive error targeted with monofocal IOLs is not mentioned. It is thus assumed that emmetropia was the goal, rather than monovision. A better question is how do patients with monovision IOL implants function compared to those with the Array [multifocal IOL] ? In my experience, patients prefer monovision! There is no glare or halo, and the quality of vision is sufficient for most to function unaided, including night driving.

Reply
Thank you for your comments. The studies in this meta-analysis recruited patients into RCTs [randomised controlled trials] comparing a multifocal lens with a monofocal lens. None of the RCTs used monovision as either a control group or intervention group. Whilst this would be an interesting study (glare and haloes may be less in the monofocal monovision group, possibly at the expense of troublesome anisometropia), this scenario is not answered by this analysis.

Contributors
Edward Pringle, review co-author

C O N T R I B U T I O N S O F A U T H O R S
For the first edition of the review, ML decided the review scope, carried out some electronic database searches, performed additional handsearches, assessed the results of searches, assessed suitability of studies, extracted data, wrote the text and updated the review.
In the 2016 edition of the review, SdeS, JE, VK and MZ screened studies, extracted data and assessed risk of bias. SdeS and JE updated the text. VK and MZ should be considered as joint 3rd authors.

D E C L A R A T I O N S O F I N T E R E S T
None known.

Internal sources
• No sources of support supplied

External sources
• National Institute for Health Research (NIHR), UK.
• Richard Wormald, Co-ordinating Editor for the Cochrane Eyes and Vision (CEV) acknowledges financial support for his CEV research sessions from the Department of Health through the award made by the NIHR to Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology for a Specialist Biomedical Research Centre for Ophthalmology.
• The NIHR also funds the CEV Editorial Base which includes part of Jennifer Evans's salary.
• The Cochrane Incentive Scheme provided funding for Jennifer Evans to assist with updating this review in 2012.
The views expressed in this publication are those of the authors and not necessarily those of the NIHR, National Health Service or the Department of Health.

D I F F E R E N C E S B E T W E E N P R O T O C O L A N D R E V I E W
The original protocol for this review was published in 2000. Since that time there have been substantive changes in recommended Cochrane Review methodology. We have added in specific information on the following methodological issues: unit of analysis, missing data and subgroup analysis.
For the update in 2016, we have collaborated with the National Institute of Care and Health Excellence (NICE) in the UK. NICE are preparing guidelines for cataract management and we agreed to work with them to ensure that the information in this review provided data relevant to the guideline. This mainly affected the comparisons and outcomes.

Types of interventions
We included an additional comparison: multifocal versus monovision. Monovision is a strategy designed to enable people to achieve good distance and near vision by adjusting the powers of the lenses such that one eye is used for distance vision and one for near vision.

Outcomes
We have added in intermediate visual acuity as an outcome. For the 2016 update, we dropped depth of focus because the data on this were sparse and difficult to interpret because of considerable variability in measurement and reporting.

Risk of bias
We used Cochrane's tool for assessing the risk of bias (replacing the Jadad scale). In the 2012 update of this review, we assessed selective outcome reporting bias by completing an outcome reporting matrix using the ORBIT classification (Kirkham 2010). In the 2016 update, we did not continue with this assessment but assessed selective outcome reporting as part of the risk of bias tool only.

Measures of treatment effect
For dichotomous outcomes, we changed the measure of effect from odds ratio to risk ratio, reflecting changing views as to the relative suitability of the risk ratio/odds ratio as a measure of effect. Although the odds ratio has some statistical advantages, it is not as easily interpreted as the risk ratio and may overestimate the effect of the intervention, particularly when the event occurs commonly within the study population.
In the 2012 update of the review, we pooled visual acuity measured on different scales using the standardised mean difference. The standardised mean difference is difficult to interpret, however, and there is accumulating evidence that different visual acuity charts perform differently at different levels of visual acuity. For these reasons, we have changed our mind about the validity of doing this. As more data were available measured on the logMAR scale we restricted our analyses to studies measuring and reporting visual acuity data on the logMAR scale. We summarised these using the mean difference.

Subgroup analysis
We have added in an additional subgroup analysis comparing unilateral and bilateral surgery.

Sensitivity analysis
Following updated guidance from Cochrane (MECIR 2013), we have added in a sensitivity analysis excluding studies at high risk of bias in one or more domains.

'Summary of findings' table
We prepared a 'Summary of findings' table, including assessing the quality of evidence using GRADE (GRADEpro 2014).

MeSH check words
Adult; Humans