Description of the condition
Age-related cataract is the leading cause of visual impairment worldwide (Quigley 2006); and cataract surgery is the most commonly performed eye operation worldwide with an estimated 19.5 million procedures carried out in 2011 (Lawless 2012a). Preferred surgical techniques have changed dramatically over the past half century with associated improvements in outcomes and safety (Riaz 2006). With this increase in safety and improvements in visual outcomes, lens extraction with intraocular lens (IOL) implantation is now increasingly performed for the treatment of other conditions, including refractive error (Packard 2005) and angle closure glaucoma (Friedman 2006).
Description of the intervention
Lasers have been used in corneal surgery for over a decade. More recently, femtosecond laser platforms that can accurately and reproducibly perform key steps in cataract surgery, including corneal incisions, capsulotomy and lens fragmentation, are now available. The potential advantages of laser assisted surgery are broad and include greater safety and better visual outcomes through greater precision and reproducibility. These systems are expensive at outset; however, the costs may be mitigated by a reduction in complication rates, less repeat surgery and better patient outcomes.
How the intervention might work
Phacoemulsification (ultrasound) is a highly successful technique first introduced over 40 years ago. It is the standard method of cataract surgery today with reported rates of major complications (posterior capsule rupture or vitreous loss) of 1.9% and overall intraoperative complication rates of approximately 4.6% (Jaycock 2007). It consists of a series of manual steps, including corneal incision creation, capsulorrhexis (circular opening of the front of the cataract lens capsule), removal of the cataract with ultrasound and placement of an IOL into the capsular bag. Each step is dependent on successful completion of the preceding steps and, therefore, surgical ability is critical to visual outcome. Laser assisted cataract surgery units can automate over half of these steps including creation of the corneal incisions (with or without additional incision to reduce astigmatism), capsulotomy and lens fragmentation facilitating lens removal. The remaining steps are removal of the fragmented crystalline lens and insertion of the IOL, which still have to be completed by hand.
While the overall range of possible operative complications in either laser assisted or manual phacoemulsification surgery are similar, rates would be expected to be lower in laser assisted procedures as laser completed steps should be more precise and more reproducible than those completed by hand. Ultimately, this should also translate to better patient outcomes. There is increasing evidence to support an advantage for laser assisted procedures with more accurate capsulotomy positioning, shape and size reported when compared to manual capsulorrhexis (Friedman 2011; Kránitz 2011; Nagy 2011). This is associated with better IOL centration (ensuring correct centering of the lens) (Nagy 2011, Kránitz 2011, Krántiz 2012) and less IOL tilt (Krántiz 2012) with fewer internal higher order aberrations (Miháltz 2011). By using a laser to fragment the crystalline lens, less phacoemulsification (ultrasound) energy is subsequently required to complete its removal. Reductions of 70% to 96% of effective phacoemulsification time (EPT) have been reported (Abell 2013a; Abell 2013b; Conrad-Hengerer 2012) with zero EPT being possible in 30% of operations in a recent series (Abell 2013b). This study also reported a 36% lower endothelial cell loss in the laser assisted procedures compared to the manual phacoemulsification (Abell 2013b). Data on the surgical learning curve (Bali 2012; Roberts 2013a) and complication rates in laser assisted cataract surgery procedures have been reported in recent large case series (Conrad-Hengerer 2012; Roberts 2013a) with the complication rates appearing favourable when compared to those from large series of manual phacoemulsification (Roberts 2013a). Studies comparing postoperative visual acuities and IOL power calculation predictability for laser assisted surgery with manual phacoemulsification procedures have shown inconsistent results with some reporting better corrected distance visual acuity (CDVA) (Krántiz 2012) and better IOL power predictability (Filkorn 2012) for laser assisted surgery, whilst others have reported no difference in CDVA (Filkorn 2012, Lawless 2012b; Miháltz 2011), uncorrected distance visual acuity (UDVA) (Lawless 2012b; Miháltz 2011) or IOL power predictability (Lawless 2012b,; Roberts 2013b).
Overall, it is anticipated that automation of several of the steps of manual phacoemulsification by using an image guided laser platform will result in fewer complications and better patient outcomes.
Why it is important to do this review
Laser assisted lens surgery platforms are now increasingly being used for lens extraction and IOL implantation. There are currently four commercially available systems: Catalys™ (OptiMedica Inc), LENSAR™ (LENSAR Inc), LenSx® (Alcon) and VICTUS™ (Bausch & Lomb Inc). The aims of this review are to compare the safety and effectiveness of laser assisted lens extraction with manual phacoemulsification.
To compare the safety and effectiveness of femtosecond laser assisted lens surgery with conventional manual phacoemulsification lens surgery.
Criteria for considering studies for this review
Types of studies
We will include all randomised controlled trials (RCTs) that meet the inclusion criteria.
Types of participants
We will include all participants who were enrolled in the respective RCT whereby either the participant or one of their eyes was randomised to either laser assisted lens surgery or manual phacoemulsification and IOL implantation. We expect participants to be adults (18 years old or more); however, we will also report separately any data from studies in younger participants.
Types of interventions
We will include all RCTs comparing laser assisted lens surgery to manual phacoemulsification, with implantation of a posterior chamber IOL in both techniques.
Types of outcome measures
Our primary outcome will be the rates of intraoperative complications in the operated eye. We anticipate that complications may be reported as overall rates of any complication, or as rates per specific complication, for example, posterior capsule tear and unplanned anterior vitrectomy (surgical removal of the vitreous humour (gel) from the middle of the eye).
- Distance visual acuity in the operated eye at least one month after initial cataract surgery. We will consider corrected distance visual acuity (CDVA) and uncorrected distance visual acuity (UDVA) separately. CDVA will demonstrate intervention safety, whilst UDVA will demonstrate intervention efficacy (see 'How the intervention might work' above). We will also consider long term data if these are reported. We anticipate visual acuity to be Early Treatment Diabetic Retinopathy Study (ETDRS) logMAR visual acuity measured at four metres under standardised conditions: however, it is unlikely that all studies will use logMAR visual acuity and we may have to account for other visual acuity measurement scales.
- Quality of vision as measured by any validated visual function score, such as the Catquest-9SF, measured at one month after initial cataract surgery.
- Any postoperative or long-term complications reported within one year of initial surgery. We anticipate these may be reported as overall rates of any complication or more specifically such as posterior capsule opacification, retinal detachment, cystoid macular oedema, corneal endothelial cell loss, corneal decompensation.
Search methods for identification of studies
We will search the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE, EMBASE, Latin American and Caribbean Health Sciences Literature Database (LILACS), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov), the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en) and the U.S. Food and Drugs Administration (FDA) website (www.fda.gov). We will not use any date or language restrictions in the electronic searches for trials.
See: Appendices for details of search strategies for CENTRAL (Appendix 1), MEDLINE (Appendix 2), EMBASE (Appendix 3), LILACS (Appendix 4), mRCT (Appendix 5), ClinicalTrials.gov (Appendix 6), the ICTRP (Appendix 7) and the FDA website (Appendix 8).
Searching other resources
We will search the reference lists of included studies to identify any additional trials. We will not handsearch conference proceedings or journals for this review.
Data collection and analysis
Selection of studies
Two authors will independently review titles and abstracts from the electronic literature searches. We will remove duplicate records and obviously irrelevant reports. We will classify the abstracts as 'exclude', 'unsure' or 'include'. We will retrieve the full text for abstracts classified as 'unsure' by both review authors, and reassess the study for inclusion. We will link together multiple reports of the same study. We will deal with potential discrepancies on unclear studies by contacting the authors for clarification and additional information. We will exclude studies labelled as 'exclude' by both review authors and will provide a reason. We will assess studies labelled 'include' for methodological quality. Any disagreement on study inclusion or exclusion will be resolved through discussion or, if this is unsuccessful, we will report it as such in the review.
Data extraction and management
Two review authors will independently extract data using a form developed by the Cochrane Eyes and Vision Group. One review author will enter data into Review Manager (RevMan 2012) following the guidelines set out in Chapter 7 of the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011a) and a second author will verify all values. If we are unable to extract all the information we are interested in from published reports, with regard to the details of the study or its numerical results, we will request the missing data from the original study investigators. We will compare the results and resolve any disagreements by discussion.
Assessment of risk of bias in included studies
Two review authors will independently assess risk of bias in the included studies using the recommended tool in Chapter 8 of the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011b). We will assess the studies for the following criteria: sequence generation and allocation concealment (selection bias), masking (blinding) of outcome assessors (detection bias), incomplete outcome data (attrition bias), selective outcome reporting (reporting bias) and other sources of bias.
We will report adequacy of random sequence generation and allocation concealment. Methods of sequence generation considered to be at low risk of bias include referring to random number tables or a list of random assignments generated by a computer. Methods at high risk of bias include sequence generation, for example, by odd or even dates of birth. Any method of allocation concealment (such as central randomisation, use of sequential numbered, opaque, sealed envelopes) which meets or exceeds the minimal criteria for judging concealment of allocation sequence (as detailed in section 8.10 of the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011b)) will be assessed as at low risk of bias. Methods such as using an open random allocation schedule may allow participants or investigators to possibly foresee assignment, thus introducing selection bias, and will be judged as high risk of bias.
We will report masking of outcome assessors by study outcomes or group of outcomes in the included studies. Masking of participants will not be possible with the interventions being examined. High risk of bias will be defined as no masking or incomplete masking, and the outcome is likely to be influenced by lack of masking; or if masking of the outcome assessor was attempted, but likely that the masking could have been broken and the outcome is likely to be influenced by a lack of masking.
We will examine for missing outcome data, rates of follow-up, reasons for losses to follow-up and analysis by the principle of intention-to-treat. We will assess whether follow-up rates for the laser assisted lens surgery and manual phacoemulsification arms were similar and whether there were missing data for the outcomes of interest. Studies will be considered at low risk of bias if, for example, there are no missing data or reasons for missing outcome data are unlikely to be related to the outcomes.
We will examine for selective reporting by comparing published reports to the study protocol, when available. We will consider a study to be at low risk of bias if the outcomes of interest are reported in the pre-specified way in both the protocol and in the published report. We will consider the risk of bias to be high if, for example, not all of the study's pre-specified primary outcomes have been reported.
The judgment for each criterion will be reported as 'satisfactory' (low risk of bias), 'unsatisfactory' (high risk of bias) or 'unclear' (insufficient information to assess). Review authors will not be masked to the report authors and trial results during the assessment. We will resolve any disagreements between the review authors by discussion. We will contact the authors of the original studies for additional information on issues that are unclear after reviewing the original study report. If there is no response from the corresponding author within four weeks, we will assess the methodological quality on the basis of the available information.
Measures of treatment effect
Our primary outcome is a dichotomous outcome (whether or not the eye suffers a complication during surgery). We plan to use the odds ratio (OR) with 95% confidence intervals (CI). For outcomes that are continuous we will use the mean difference (MD) between comparison groups with 95% confidence intervals.
Unit of analysis issues
Cataract can be bilateral but immediate sequential bilateral surgery is not routinely conducted in the UK. However, it would still be possible to have a paired study (using both eyes from a patient) and operating on the second eye within perhaps two weeks of the first operation. Therefore, our review may include a mixture of single eye studies and studies which have included both eyes of patients. In the latter case, it is possible that one eye will receive one procedure and the other eye the other procedure or that both eyes will receive the same treatment. We will document which design has been used and we will then record whether study authors have stated explicitly why they have opted for a particular design. If one eye has been chosen but both were eligible, we will document how the study eye was selected. If both eyes are included we will record how each eye was randomised, or whether the first eye was randomised and the second automatically received the alternate treatment. Each type of study may need analysing separately and then estimates from the different types of studies will be combined using the generic inverse variance method.
Dealing with missing data
Where any data in regard to the details of the study and its numerical results are missing, we will contact the original investigators. If the corresponding author does not respond within four weeks, we will extract data as available from the published report. We will refer to guidelines in Chapter 16 of the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011c) for handling missing data. We will collect data on the reason for missingness and will examine whether or not missing rates are similar between comparison groups and whether reasons are similar between groups.
Assessment of heterogeneity
We will check for statistical heterogeneity by examining the forest plots of results of the studies and by examining the I
Assessment of reporting biases
If sufficient trials are identified (10 or more), we will examine the relevant funnel plots for signs of asymmetry in Review Manager (RevMan 2012).
We will perform data analysis according to Chapter 9 of the Cochrane Handbook for Systematic Reviews of Interventions (Deeks 2011). We aim to use a random-effects model unless there are less than three studies which presents problems in estimating a random-effects model. In this case we may use a fixed-effect model but will compare the findings between fixed-effect and random-effects models in this scenario. If we consider heterogeneity to be substantial we will not conduct a meta-analysis but will instead provide a narrative interpretation of our results.
Subgroup analysis and investigation of heterogeneity
To date there are four commercially available femtosecond laser cataract surgery systems: Catalys™ (OptiMedica Inc), LENSAR™ (LENSAR Inc), LenSx® (Alcon) and VICTUS™ (Bausch & Lomb Inc) and it is possible that outcomes may differ between manufacturers. Consequently, studies may need analysing separately by the laser platform used.
If there are enough trials contributing to the meta-analyses we will investigate the effect of excluding studies judged to be at high risk of bias.
The Cochrane Eyes and Vision Group (CEVG) will create and execute the electronic searches. We thank Jennifer Evans and Stephanie Watson for their comments on this protocol and Anupa Shah for her assistance throughout the editorial process.
Richard Wormald (Co-ordinating Editor for CEVG) acknowledges financial support for his CEVG research sessions from the Department of Health through the award made by the National Institute for Health Research to Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology for a Specialist Biomedical Research Centre for Ophthalmology. The views expressed in this publication are those of the authors and not necessarily those of the Department of Health.
Appendix 1. CENTRAL search strategy
#1 MeSH descriptor: [Phacoemulsification] this term only
#3 phaco or phako
#4 #1 or #2 or #3
#5 MeSH descriptor: [Lasers] explode all trees
#8 #5 or #6 or #7
#9 manual* or standard*
#10 #4 and #8 and #9
Appendix 2. MEDLINE (OvidSP)
1. randomized controlled trial.pt.
2. (randomized or randomised).ab,ti.
9. exp animals/
10. exp humans/
11. 9 not (9 and 10)
12. 8 not 11
15. (phaco or phako).tw.
17. exp lasers/
21. (manual$ or standard$).tw.
22. 16 and 20 and 21
23. 12 and 22
The search filter for trials at the beginning of the MEDLINE strategy is from the published paper by Glanville et al (Glanville 2006).
Appendix 3. EMBASE (OvidSP)
1. exp randomized controlled trial/
2. exp randomization/
3. exp double blind procedure/
4. exp single blind procedure/
7. (animal or animal experiment).sh.
9. 7 and 8
10. 7 not 9
11. 6 not 10
12. exp clinical trial/
13. (clin$ adj3 trial$).tw.
14. ((singl$ or doubl$ or trebl$ or tripl$) adj3 (blind$ or mask$)).tw.
15. exp placebo/
18. exp experimental design/
19. exp crossover procedure/
20. exp control group/
21. exp latin square design/
23. 22 not 10
24. 23 not 11
25. exp comparative study/
26. exp evaluation/
27. exp prospective study/
28. (control$ or prospectiv$ or volunteer$).tw.
30. 29 not 10
31. 30 not (11 or 23)
32. 11 or 24 or 31
35. (phaco or phako).tw.
37. exp laser/
41. (manual$ or standard$).tw.
42. 36 and 40 and 41
43. 32 and 42
Appendix 4. LILACS search strategy
phacoemulsif$ or phakoemulsif$ or phaco or phako and laser$ or femtosecond and manual$ or standard$
Appendix 5. metaRegister of Controlled Trials search strategy
(phacoemulsification or phakoemulsification or phaco or phako) AND (laser OR femtosecond)
Appendix 6. ClinicalTrials.gov search strategy
(Phacoemulsification OR Phakoemulsification OR Phaco OR Phako) AND (Laser OR Femtosecond)
Appendix 7. ICTRP search strategy
phacoemulsification OR phakoemulsification OR phaco OR phako = Title AND laser OR femtosecond = Intervention
Appendix 8. FDA search strategy
phacoemulsification AND laser OR femtosecond AND manual OR standard AND random OR randomly OR randomised OR randomized
Contributions of authors
ACD and CB contributed to the concept, design and writing of the protocol. DMG contributed to the design and provided feedback for the protocol. All authors contributed to responding to editorial and peer review comments.
Declarations of interest
Sources of support
- NIHR, UK.CB acknowledges financial support from the Department of Health through the award made by the National Institute for Health Research to Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology for a Specialist Biomedical Research Centre for Ophthalmology. The views expressed in this publication are those of the authors and not necessarily those of the Department of Health.
- No sources of support supplied