Trifocal intraocular lenses versus bifocal intraocular lenses after cataract extraction
Abstract
This is a protocol for a Cochrane Review (Intervention). The objectives are as follows:
The objective of this review is to assess the visual effects of implantation of trifocal intraocular lenses compared with bifocal intraocular lenses during cataract surgery among presbyopic patients.
Background
Description of the condition
The lens is one of the most important tissues in the human eye. Located in the posterior chamber, it is the second most powerful refractive structure and it contributes 20% to 30% of the total refractive power. It is an elastic and transparent tissue that helps focus images onto the retina. When there is a change of refractive power to the lens, the accommodation process causes the lens to change its anterio‐posterior length and is associated with convergence and miosis (Glasser 1999). This process allows adequate intermediate and near vision.
The theory of accommodation that is broadly accepted is the Helmholtz theory, in which accommodation is the result of elastic properties of the human lens and possibly the vitreous that allows the lens to increase its negative power when zonular tension is relieved and vice versa. This movement is performed by the ciliary muscle. This property of the human lens is lost during aging in a progressive manner until the accommodation range is practically none (Glasser 1999; Torricelli 2012).
With aging, accommodation decreases, a process known as presbyopia. In patients with presbyopia, the ability of the lens to accommodate is insufficient for near vision. This process generally occurs between age 40 and 50 years (Glasser 1999; Papadopoulos 2014). The impact on quality of life for presbyopia patients is significant (Torricelli 2012).
As presbyopia develops and elasticity is lost, the lens may become opaque. The loss of transparency of the lens is called cataract. There are several types of cataracts. The most common type is the senile (age‐related) cataract. There are several well known risk factors for developing this type of vision‐impairing lens opacity, such as high sodium intake (Bae 2015), some systemic diseases such as diabetes mellitus (Li 2014), high body mass index (WHO 2015), exposure to ultraviolet B radiation, and smoking (Hodge 1995).
According to the World Health Organization, cataract accounts for 51% of worldwide blindness and affects about 20 million people around the world (WHO 2015).
Symptoms associated with this condition are myopia and decreases in contrast sensitivity and visual acuity. Extraction of the cataractous lens by phacoemulsification followed by capsular bag implantation of an artificial intraocular lens (IOL) is the current standard of care of patients with this problem (Carson 2014). Reliance on spectacles to correct residual refractive errors for distance visual acuity resulting from removal of the natural lens rarely occurs in the developed world because they usually are corrected by the IOL.
Description of the intervention
Cataract surgery is performed to extract the cloudy lens material, while preserving some structures such as the capsular bag. Artificial intraocular lenses are then placed to restore vision in an eye (Kohnen 2009). The standard practice is implantation of a monofocal IOL, which confers only one focal point on the retina (Carson 2014). With a monofocal IOL, a pseudophakic patient continues to be presbyopic, since a monofocal IOL corrects only one focal point, typically to provide good distance vision; thus, spectacles may still be needed after phacoemulsification surgery to restore vision at other distances. As modern technology advances and expectations of better vision increase, the goal of cataract surgery is no longer purely to restore vision; the refractive component is also an important aspect prior, during and after surgery (Torricelli 2012). Multifocal lenses were designed to give more than one focal point to offer spectacle independence to the patient.
With changes in social and work environments, especially use of computers, tablets, smartphones, etc., excellent intermediate distance vision has become more important. New types of IOL design feature a refractive and diffractive component, and confer three focal points within the eye. These trifocal IOLs restore near, far and intermediate vision (Gatinel 2013). IOLs with this design have been shown to achieve better patient satisfaction (Kretz 2015b).
How the intervention might work
Different multifocal IOLs have been developed. Diffractive IOLs originally were designed to divide light in order to have two or more focal points to restore near, far and intermediate vision in comparison to monofocal IOLs. These results were obtained by using apodization and convolution technologies. Three focal points may be preferable in an IOL because it restores near, intermediate and far vision.
Multifocal acrylic IOLs come in several designs. With the first generation of multifocal lens design, the goal was for the lenses to restore two focal points, for far and near vision (Voskresenskaya 2010). This bifocal intraocular lens, which by convention is called a multifocal lens, has acceptable visual outcomes and gives independence of spectacles to many pseudophakic people (Calladine 2012; Torricelli 2012). The latest generation multifocal intraocular lenses are based on a diffractive/refractive technology design and have as their main objective restoring intermediate vision also (Papadopoulos 2014).
Different bifocal IOLs have different visual outcomes, mainly because of different add power placed in the IOL to adjust for different near vision distances. Besides near and distance vision, good intermediate vision is needed to increase patient satisfaction with IOLs (Kretz 2015a; Kretz 2015b). A few trifocal intraocular lenses are available. Excellent visual outcomes and high patient satisfaction scores have been reported with these lenses (Voskresenskaya 2010; Cochener 2012; Lesieur 2012; Torricelli 2012; Sheppard 2013; Vryghem 2013; Law 2014).
The most common adverse visual effects in a multifocal intraocular lens are glare, halos and loss of contrast sensitivity that result in poor quality of vision during mesopic conditions (Carson 2014). These effects seem to be inherent to the multifocal lens design and there is a period of neuroadaptation when the brain and visual system adopts a new way of seeing. As this process evolves, patients become more comfortable with their new vision and their perception of side effects decreases (Voskresenskaya 2010).
Why it is important to do this review
It is important to restore visual acuity at all distances in order to treat cataract and presbyopia satisfactorily. Adverse effects, such as halos, glare, lowered contrast sensitivity and dissatisfaction associated with IOLs, seem to be inherent to the multifocal design (bifocal or trifocal IOL). However, other visual and patient‐important benefits have been reported for both bifocal and trifocal IOLs (Voskresenskaya 2010; Cochener 2012; Lesieur 2012; Sheppard 2013; Vryghem 2013; Law 2014). Another Cochrane systematic review comparing multifocal versus monofocal intraocular lenses after cataract extraction was published in 2012 (Calladine 2012), but to our knowledge, no high‐quality systematic review of evidence about comparison of trifocal IOLs and bifocal IOLs has been published.
Objectives
The objective of this review is to assess the visual effects of implantation of trifocal intraocular lenses compared with bifocal intraocular lenses during cataract surgery among presbyopic patients.
Methods
Criteria for considering studies for this review
Types of studies
We will include only randomized controlled trials (RCTs). We will include all eligible trials regardless of their publication status or language of publication.
Types of participants
We will include trials in which the participants were older than 30 years with cataract and presbyopia. We will document when trials included participants with other ocular comorbidities, such as pseudoexfoliation syndrome, glaucoma, diabetes mellitus, age‐related macular degeneration, retinal disease, optic nerve disease, or amblyopia in the eye undergoing cataract surgery or a history of intraocular surgery, pediatric cataract or ocular trauma.
Types of interventions
We will include studies in which implantation of trifocal IOLs were compared with implantation of bifocal IOLs during cataract surgery.
Types of outcome measures
Primary outcomes
The primary outcome of this review will be mean uncorrected (without the aid of spectacles or contact lenses) distance visual acuity measured by LogMAR chart at one‐year follow‐up.
Secondary outcomes
The secondary outcomes for this review will include:
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mean uncorrected distance visual acuity measured by LogMAR chart at three‐month and six‐month follow‐up;
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mean uncorrected near visual acuity at three‐month, six‐month, and one‐year follow‐up;
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mean uncorrected intermediate visual acuity at three‐month, six‐month, and one‐year follow‐up;
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mean best‐corrected distance visual acuity at three‐month, six‐month, and one‐year follow‐up;
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mean contrast sensitivity, measured by the FACT (Functional Acuity Contrast Test) chart (Pesudovs 2004), or by the Pelli‐Robson contrast sensitivity test (Mantyjarvi 2001) noted in LogCS at different cycles per grade in spatial frequencies at three‐month, six‐month, and one‐year follow‐up;
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mean quality of life or visual function evaluated by validated and comparable instruments (e.g. NEI‐VFQ25) noted in numeric scores at three‐month, six‐month, and one‐year follow‐up.
Adverse outcomes
A) visual disturbances such as glare, experienced when a source of light other than the main target image illuminates the retina, and halos, defined as visual disturbances related to the main target image that lower contrast sensitivity; these visual disturbances are only noted by proportions at three, six and twelve months after surgery.
B) opacification of the posterior capsule (proliferation of epithelial lens cells in the main visual axis that lowers visual acuity), with or without YAG laser capsulotomy, at three, six and twelve months after surgery.
We will assess additional adverse effects related to IOLs mentioned in any of the included studies.
Search methods for identification of studies
Electronic searches
The Cochrane Eyes and Vision Information Specialist will search the following electronic databases for randomised controlled trials and controlled clinical trials. There will be no language or publication year restrictions.
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Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) in the Cochrane Library (latest issue) (Appendix 1);
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MEDLINE Ovid (1946 to present) (Appendix 2);
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Embase.com (1947 to to present) (Appendix 3);
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PubMed (1948 to to present) (Appendix 4);
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LILACS (Latin American and Caribbean Health Science Information Database (1982 to present) (Appendix 5);
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US National Institutes of Health Ongoing Trials Register ClinicalTrials.gov (www.clinicaltrials.gov) (Appendix 6);
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World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp) (Appendix 7);
Searching other resources
We will search the reference lists of the retrieved articles and the abstracts from the Annual Meeting of the Association for Research in Vision and Ophthalmology (ARVO) for the years 2005 to 2015 for other relevant studies that compare outcomes after implantation of trifocal and bifocal IOLs.
Data collection and analysis
Selection of studies
Two authors working independently will assess the titles and abstracts of all records identified by the electronic and manual searches. Each author will review and label each record as 'definitely relevant', 'possibly relevant' or 'definitely not relevant.' We will resolve any differences between the two authors by discussion. We will retrieve the full‐text report for all records labeled as 'definitely relevant' or 'possibly relevant.' Two authors working independently will assess each full‐text report and classify as 'include,' 'exclude,' or 'awaiting classification.' We will resolve any differences between the two authors by discussion. We will document the studies excluded after review of the full‐text report and note why they did not meet inclusion criteria.
Data extraction and management
Two authors independently will extract data from reports of included studies using a data collection form developed by Cochrane Eyes and Vision. Two review authors will check the data independently before it is entered into Review Manager 5 software (RevMan 2014). We will record the following characteristics of included studies: study methods, participants, interventions, and outcomes. Where information about (or outcome data from) included studies are missing or unclear, we will contact the study investigators, or organizations involved, for additional data, confirmation or clarification. We will collect and use the most detailed numerical data available from included studies to facilitate analyses. We will attempt to obtain data from available reports, investigators, or organizations in preference to less precise methods such as extracting numeric data from graphs. If it should be necessary to extract data available only in graphical displays, two review authors will extract the data independently and resolve any disagreement or discrepancy by discussion or by consulting a third review author.
Assessment of risk of bias in included studies
We will use the latest version of the Cochrane 'Risk of bias' tool as described in Chapter 8 of the Cochrane Handbook for Systematic Reviews of Interventions to assess the risk of bias and assign judgments of this for included studies (Higgins 2011). Two authors will independently make 'Risk of bias' assessments for each included RCT. They will grade each parameter of trial quality as 'low risk of bias', 'high risk of bias' or 'unclear risk of bias'. We will judge selection bias (sequence generation and allocation concealment before assignment), performance bias (masking of participants and study personnel), detection bias (masking of outcomes assessors), attrition bias (loss to follow‐up), reporting bias (selective outcome reporting), and other sources of bias. Whenever any of the above domains is graded as 'unclear risk of bias' we will contact the investigators of the published RCT reports in order to obtain clarification. In case of failure to communicate with any of the study investigators, we will assess the methodological quality of the trial based on the available information. We will resolve any disagreements on the above assessments between the authors by discussion until consensus is reached or by consulting another review author.
Measures of treatment effect
Continuous outcomes
Standardized mean differences (SMDs) and 95% confidence intervals (CIs) will be calculated for continuous data outcomes whenever different instruments of measurement are employed in different studies. For example, we will use this statistic when distance and near visual acuity are reported on different scales (LogMAR, decimal, or Snellen fraction) in different studies to permit analyzing effects on a uniform scale (Deeks 2011). Where possible, we will check for skewness using the method outlined in Chapter 9 of the Cochrane Handbook for Systematic Reviews of Interventions (Deeks 2011). If the same instrument (for example the National Eye Institute Visual Function Questionnaire (NEI‐VFQ25)) is used in all studies that contribute data to a meta‐analysis, the overall effects will be estimated by mean differences (MDs) and 95% CIs since these values are known as continuous data outcomes.
Dichotomous Outcomes
Adverse outcome such, as 'glare,' 'halos,' 'spectacle independence,' 'posterior capsular opacification' (PCO) and 'glistenings' will be analyzed as dichotomous outcomes. We will calculate risk ratios (RRs) and 95% CIs to estimate effects.
Unit of analysis issues
The population targeted for this review is patients with cataract and presbyopia. We may identify and include studies in which the participants have had IOLs placed in both eyes on the same day. We will review all reports from such studies to ensure that the authors dealt with this situation appropriately by using statistical measures that account for this correlation of outcomes between eyes. Since our goal is to compare trifocal versus bifocal IOLs, studies in which any combination of both IOL types in individual patients or eyes was employed will be excluded.
Dealing with missing data
We expect to analyze outcomes on an intention‐to‐treat basis. Whenever outcome data are missing for some participants , we will contact the authors to confirm which data were used for analysis. We will only analyze available data. We will not impute data for purposes of this review.
Assessment of heterogeneity
We will investigate clinical or methodological heterogeneity among studies by evaluating differences among included studies with respect to characteristics of participant populations, interventions and outcome assessment. We will evaluate statistical heterogeneity among outcomes by examining the overlap in confidence intervals in forest plots and using the Chi² and the I² statistic as defined in Chapter 9 of the Cochrane Handbook for Systematic Reviews of Interventions (Deeks 2011). We will use the I² statistic to assess the proportion of total variability explained by heterogeneity between studies. If substantial heterogeneity (I² greater than 60%) or inconsistency among effect sizes estimated from individual studies contributing data to a meta‐analysis is observed, we will not report a pooled analysis. Rather, we will provide a narrative summary of the intervention effects estimated from individual studies.
Assessment of reporting biases
We will use funnel plots to assess publication bias in reported studies when a sufficient number of trials (more than 10) are included in the review.
Data synthesis
We will make comparisons between any bifocal IOL versus any trifocal IOL. We will analyze data according to the guidelines set out in Chapter 9 of the Cochrane Handbook for Systematic Reviews of Interventions (Deeks 2011). As long as there is no statistical or clinical heterogeneity, or fewer than three trials contribute data to a meta‐analysis, we will use a fixed‐effect model to estimate intervention effects. Otherwise we will use random‐effects models.
When sufficient data are available, we will perform a meta‐analysis for each of the following outcomes: visual acuity at different distances — far, intermediate and near — at one month, six months and twelve months after cataract surgery. Contrast sensitivity values will be assessed at three, six, and twelve months after the surgery.
We will compare the proportions of adverse outcomes reported with each type of IOL, such as glare, halos, glistenings, posterior capsule opacification and any other adverse event reported from the included studies at any follow‐up time from the first day after surgery to 18 months after surgery.
Subgroup analysis and investigation of heterogeneity
We will investigate potential explanations of clinical or statistical heterogeneity by comparing outcomes within subgroups of participants defined by factors such as unilateral versus bilateral surgery, and optical design in the IOLs whenever sufficient data have been reported from the included studies.
Sensitivity analysis
We will examine the impact of excluding trials with high risk of bias, unpublished data, and industry funding to assess the robustness of estimates with respect to these factors.
Summary of findings
We will prepare a 'Summary of findings' table to present the estimated effects of trifocal IOLs versus bifocal IOLs at one‐year follow‐up. The outcomes to be included in the table are 1) mean uncorrected distance visual acuity, 2) mean uncorrected near visual acuity, 3) mean uncorrected intermediate visual acuity, 4) mean best‐corrected distance visual acuity, 5) mean contrast sensitivity, 6) mean quality of life or visual function scores, and 7) adverse events. We will include our assessment of the certainty of the available evidence for each outcome using the GRADE approach (Langendam 2013). Two authors independently will judge each outcome to confer very low, low, moderate, or high certainty evidence. We will resolve any differences between the two authors by discussion.
