Evidence-based Synthesis Program Department of Veterans Affairs

Health Services Research & Development Service

Benefits and Harms of Femtosecond 

Laser Assisted Cataract Surgery: 

A Systematic Review

December 2013

Prepared for:

Department of Veterans Affairs

Veterans Health Administration

Health Services Research & Development Service

Washington, DC 20420

Prepared by:

Evidence-based Synthesis Program (ESP) Center

Portland VA Medical Center

Portland, OR

Devan Kansagara, M.D., M.C.R., Director

Investigators:

Principal Investigator: 

Ana Quiñones, Ph.D.

Co-Investigators: 

Ken Gleitsmann, M.D., M.P.H. 

Michele Freeman, M.P.H. 

Rochelle Fu, Ph.D.

Maya O’Neil, Ph.D. 

Makalapua Motu’apuaka, B.S.

Devan Kansagara, M.D., M.C.R.

4
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PREFACE

Quality Enhancement Research Initiative’s (QUERI) Evidence-based Synthesis Program 

(ESP) was established to provide timely and accurate syntheses of targeted healthcare topics 

of particular importance to Veterans Affairs (VA) managers and policymakers, as they work to 

improve the health and healthcare of Veterans. The ESP disseminates these reports throughout 

VA.

QUERI provides funding for four ESP Centers and each Center has an active VA affiliation. The 

ESP Centers generate evidence syntheses on important clinical practice topics, and these reports 

help:

• develop clinical policies informed by evidence,

• guide the implementation of effective services to improve patient

outcomes and to support VA clinical practice guidelines and performance

measures, and

• set the direction for future research to address gaps in clinical knowledge.

In 2009, the ESP Coordinating Center was created to expand the capacity of QUERI Central 

Office and the four ESP sites by developing and maintaining program processes. In addition, 

the Center established a Steering Committee comprised of QUERI field-based investigators, 

VA Patient Care Services, Office of Quality and Performance, and Veterans Integrated Service 

Networks (VISN) Clinical Management Officers. The Steering Committee provides program 

oversight, guides strategic planning, coordinates dissemination activities and develops 

collaborations with VA leadership to identify new ESP topics of importance to Veterans and the 

VA healthcare system.

Comments on this evidence report are welcome and can be sent to Nicole Floyd, ESP 

Coordinating Center Program Manager, at nicole.floyd@va.gov.

Recommended citation: Quiñones A, Gleitsmann K, Freeman M, Fu R, O’Neil M, Motu’apuaka 

M, Kansagara D. Benefits and Harms of Femtosecond Laser Assisted Cataract Surgery: A 

Systematic Review. VA-ESP Project #05-225; 2013.

This report is based on research conducted by the Evidence-based Synthesis Program 

(ESP) Center located at the Portland VA Medical Center, Portland OR funded by the 

Department of Veterans Affairs, Veterans Health Administration, Office of Research 

and Development, Health Services Research and Development. The findings and 

conclusions in this document are those of the author(s) who are responsible for its 

contents; the findings and conclusions do not necessarily represent the views of the 

Department of Veterans Affairs or the United States government. Therefore, no statement 

in this article should be construed as an official position of the Department of Veterans 

Affairs. No investigators have any affiliations or financial involvement (e.g., employment, 

consultancies, honoraria, stock ownership or options, expert testimony, grants or patents 

received or pending, or royalties) that conflict with material presented in the report.
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TABLE OF CONTENTS 

EXECUTIVE SUMMARY

Background.................................................................................................................................................... 1

Methods......................................................................................................................................................... 1

Results ........................................................................................................................................................... 2

Discussion...................................................................................................................................................... 3

Conclusion..................................................................................................................................................... 4

Summary of evidence table on the effects of femtosecond laser assisted cataract surgery ........................... 5

BACKGROUND .................................................................................................................................................. 6

METHODS

Topic Development........................................................................................................................................ 7

Search Strategy............................................................................................................................................ 11

Study Selection............................................................................................................................................ 11

Data Abstraction .......................................................................................................................................... 11

Study Quality............................................................................................................................................... 12

Rating the Body of Evidence ....................................................................................................................... 12

Data Synthesis............................................................................................................................................. 12

RESULTS

Literature Flow ............................................................................................................................................ 13

Key Question 1: What is the evidence that FLACS is associated with better patient outcomes than 

conventional cataract surgery? ...................................................................................................... 15

Key Question 2a: What are the adverse effects that have been reported for FLACS? ................................ 18

Key Question 2b: What is the evidence that FLACS is associated with a lower risk of adverse 

effects than conventional cataract surgery? .................................................................................. 19

Key Question 3: What is the evidence that the experience of the surgeon is associated with 

adverse effects of FLACS? ........................................................................................................... 20

Ongoing Studies .......................................................................................................................................... 21

DISCUSSION ...................................................................................................................................................... 29

Future Studies.............................................................................................................................................. 31

Conclusions ................................................................................................................................................. 32

REFERENCES ................................................................................................................................................... 33

TABLES

Table 1: Characteristics and findings of studies of femtosecond laser assisted cataract surgery ......... 22

Table 2: Characteristics of upcoming studies presented at recent conference proceedings or 

registered on ClinicalTrials.gov ............................................................................................. 26

Table 3: Summary of the evidence on the effects of femtosecond laser assisted cataract surgery ...... 32
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FIGURES

Figure 1: Analytic Framework .............................................................................................................. 10

Figure 2: Femtosecond laser assisted cataract surgery - literature flow diagram .................................. 14

Figure 3: Corrected distance visual acuity (CDVA) in studies comparing femtosecond laser with 

conventional cataract surgery................................................................................................. 17

Figure 4: Effective phacoemulsification time (EPT) in studies comparing femtosecond laser with 

conventional cataract surgery................................................................................................. 17

APPENDIX A: SEARch StRAtEGy .............................................................................................................. 37

APPENDIX B: INclUSIoN/EXclUSIoN cRItERIA .................................................................................... 39

APPENDIX c: ElIGIBIlIty chARActERIStIcS oF StUDIES (PICOTS tABlE) ............................. 40

APPENDIX D: ASSESSmENt oF mEthoDoloGIc QUAlIty IN StUDIES 

oF FEmtoSEcoND lASER ASSIStED cAtARAct SURGERy ......................................... 41

APPENDIX E: PEER REvIEw commENtS AND RESPoNSES .................................................................. 45
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EXECUTIVE SUMMARY

BACKGROUND

The preferred method of removing cataracts in the developed world is phacoemulsification. 

Using this technique, ultrasonic energy softens the dense lens material of the cataract, which 

is then extracted from the eye with suction and irrigation. Current practice includes creating 

manual corneal incisions and anterior capsulotomies, followed by phacoemulsification. Recently 

these three manual procedures have been performed in an automated fashion with the use of 

the femtosecond laser (FSL). Several FSL systems have been approved by the FDA for use in 

the U.S. for some or all of these procedural steps in cataract surgery. FSL technology has been 

widely used in various refractive surgery applications in recent years. Studies have suggested 

decreased phacoemulsification energy use with FSL cataract surgery and have examined the 

potential advantages of more precise corneal incisions and capsulotomy formation. 

Cataract surgery is a frequently performed operation in the VHA, with more than 49,000 

performed in 2012. As a result, the VHA National Surgery Office has been tasked with making 

a recommendation regarding whether femtosecond lasers provide appropriate cost-benefit and 

risk-benefit ratios to support implementation for cataract surgery in the VA. The purpose of 

this systematic review is to examine the effectiveness and safety of femtosecond laser assisted 

cataract surgery (FLACS) relative to conventional cataract surgery. Key questions were 

developed in conjunction with the stakeholders which address the effectiveness, safety, adverse 

consequences and economic implications of adopting FLACS into the VA system.

METHODS

We conducted a primary review of the literature by systematically searching, reviewing 

and analyzing the scientific evidence as it pertains to the research questions. To identify 

relevant articles, we began by searching MEDLINE®, CINAHL and the Cochrane Database 

of Systematic Reviews. We further evaluated the bibliographies of included primary studies 

and any systematic or nonsystematic reviews that were identified. To identify in-progress or 

unpublished studies, we searched ClinicalTrials.gov. We also searched conference proceedings 

of ophthalmologic societies and topic specific journals, including the following: The American 

Society of Cataract and Refractive Surgery; Journal of Cataract & Refractive Surgery; American 

Academy of Ophthalmology; Ophthalmology; International Society of Refractive Surgery; 

American Academy of Ophthalmic Executives; The Foundation of the American Academy of 

Ophthalmology, The Royal College of Ophthalmologists; COS Conference Papers Index; and 

Proceedings First (OCLC).

Two reviewers trained in the critical analysis of literature assessed for relevance the abstracts 

of citations identified from literature searches. Two reviewers independently assessed full-text 

articles for inclusion; disagreements were resolved through consensus. We assessed the quality 

of each study using published tools. We assessed the overall quality of the body of evidence 

for each outcome using a method developed by the Grades of Recommendation, Assessment, 
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Development and Evaluation (GRADE) Working Group. We critically analyzed the evidence on 

effectiveness and adverse effects and compiled a narrative synthesis of findings. We conducted 

meta-analyses of two commonly reported outcomes in FSL and conventional cataract surgery 

procedures, corrected distance visual acuity (CDVA) and effective phacoemulsification time 

(EPT). 

RESULTS

We reviewed 468 titles and abstracts from the electronic search and identified 436 additional 

references through manual searching of reference lists, input from technical advisors and 

reviewing conference proceedings of ophthamalogic societies for recent unpublished or ongoing 

studies. 

After applying inclusion/exclusion criteria at the abstract level, seventy full-text articles were 

reviewed, as shown in Figure 2. Of the full-text articles, we rejected fifty-four that did not meet 

our inclusion criteria.

Key Question 1: What is the evidence that FLACS is associated with better 

outcomes than conventional cataract surgery?

We identified nine studies addressing the comparative effectiveness of FLACS versus 

conventional surgery, including three small to medium-sized randomized controlled trials. Six of 

these studies (and all three of the randomized controlled trials) were conducted at Semmelweis 

University, Budapest, Hungary, all surgeries having been performed by the same surgeon, using 

the Alcon LenSx laser. Two studies were conducted in an ophthalmology group practice, at 

Launceton Eye Hospital, Tasmania, Australia, using the OptiMedica Catalys laser. Sample sizes 

in these studies ranged from 25 to 400 patients, with follow-up periods extending from two 

weeks to one year. 

The most commonly reported relevant outcomes in these comparative studies were: postoperative corrected distance visual acuity (CDVA) and effective phacoemulsification time (EPT). 

We conducted a meta-analysis of CDVA and EPT, but heterogeneity precluded calculation of 

a reliable summary effect estimate. The results of individual studies are presented in Figures 

3 and 4. Overall, there was low evidence of benefit from three randomized controlled trials 

and six observational studies. There were no significant differences noted between groups for 

CDVA outcomes. EPT outcomes were mixed, with results either comparable between FSL and 

conventional cataract surgery groups or favoring FSL groups. No studies addressed quality of 

life measures. Methodological concerns were noted regarding the generalizability of studies 

conducted from limited sites and potential sample selection bias from enrollment into FSL and 

conventional surgery groups.

Key Question 2a: What are the adverse effects that have been reported for 

FLACS? 

Seven studies were identified addressing adverse effects, unique to FLACS. Sample sizes 

in these studies ranged from 25 to 1300 patients, with follow-up periods extending from 

immediately following the procedure, to three months post-operative. 
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We grouped the adverse event outcomes in these studies by either: 1) those occurring as a 

result of difficulties with the laser-patient interface, or 2) the change in intraocular pressure 

(IOP) measured during the FLACS procedure. Five studies reported difficulties related to the 

laser interface with the ocular surface (including the orbital structures). Two studies measured 

intraocular pressure (IOP) fluctuation during FLACS procedures. A small proportion of patients 

experienced suction breaks, second docking attempts and aborted procedure adverse events. 

FSL application is also associated with an increase in IOP. Overall, we found moderate to low 

strength of evidence for adverse events with methodological concerns raised from enrollment 

criteria used for FSL surgery groups. 

Key Question 2b: What is the risk of adverse effects from FLACS compared to the 

risk associated with conventional cataract surgery?

Nine studies addressed the adverse effects of FLACS compared to conventional cataract surgery. 

Sample sizes in these studies ranged from 25 to 400 patients, with follow-up periods extending 

from one week to one year. 

We grouped the adverse event outcomes of these studies by the ocular structures which were 

affected. Five of these studies reported, variously: capsulotomy configuration, position and the 

resultant effects on IOL decentration and refractive outcomes. Two of these studies reported 

post-operative corneal edema by measuring either corneal thickness or corneal endothelial cell 

loss. An additional two studies compared post-operative macular thickness and morphology, as 

measured by optical coherence tomography (OCT). The FSL and control groups were similar 

for post-operative corneal thickness and macular edema measurements, with corneal endothelial 

cell loss decreased in the FSL group in one study. Overall, we found moderate to low strength of 

evidence for comparative adverse events with methodological concerns from enrollment criteria 

used for the FSL and conventional surgery groups.

Key Question 3: What is the evidence that the experience of the surgeon is 

associated with adverse effects of FLACS?

Three studies reported outcomes relevant to the experience of the surgeon in performing 

the FLACS procedure. Sample sizes in these studies ranged from 200 to 1300 patients, with 

follow-up periods extending from two weeks to three months. Overall, one of the studies found 

no significant differences between outcomes for initial and subsequent groups of patients 

undergoing FLACS, while on the other hand, two studies from the same team of researchers 

found significantly fewer complications associated with greater experience with FLACS. 

There were methodological concerns from enrollment criteria used for the FSL and conventional 

surgery groups.

DISCUSSION

We found no evidence that FLACS differs from conventional cataract surgery on measures of 

safety and effectiveness. The unique risks associated with FLACs are primarily related to laser 

docking interface difficulties, which may be reduced with increasing surgical experience with 

the procedure. The comparative adverse event risks of FLACS and conventional surgery were 
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similar. Complications rates in FLACS cohorts were found to be reduced or unchanged by 

surgical experience in the included studies of this review.

We found moderate evidence of comparable CDVA outcomes between FLACS and conventional 

cataract surgery groups. We noted limited evidence for a reduction of EPT in the FSL compared 

to the conventional cataract surgery group. Furthermore, meta-analyses found no statistically 

significant differences between FSL and conventional groups in either CDVA or EPT. No studies 

reported findings related to quality of life outcomes or cost effectiveness of FLACS relative to 

conventional cataract surgery.

Most of the included studies reported on the comparative risks of adverse effects between FSL 

and conventional cataract surgery. Reports of adverse events were similar between FSL and 

conventional groups, including IOL positioning, corneal thickness, macular edema and residual 

refractive error. The association between the experience of the surgeon and FLACS adverse 

effects was limited to three eligible studies, two of which were conducted by the same team of 

researchers. These studies reported mixed results of surgical experience reducing the incidence 

of FLACS adverse events.

There were methodological concerns for the included studies that represent potential sources 

of bias that threaten the validity of study findings. Many studies had small to medium sample 

sizes. Study methods were often unclear, particularly with regard to the application of inclusion 

and exclusion criteria for FSL treatment groups and the enrollment of treatment and control 

cohorts. Studies often excluded patients with denser cataracts, comorbidities and those deemed 

uncooperative from the FSL treatment groups. In addition, many study protocols centered around 

patients self-selecting into FSL or conventional surgery groups. 

The majority of included studies (all but two) report financial conflicts of interest, with included 

studies clustered around a limited number of geographic sites, conducted by the same team of 

coauthors. All four of the included randomized trials were conducted by the same research group 

and every surgery (FSL or conventional) was completed by the same surgeon, who was also 

a study co-author. It is also unclear whether or not there was any overlap in the study patient 

populations of these trials, given they are conducted at the same site and at what appeared to be a 

similar timeframe.

CONCLUSION

This systematic review found visual outcomes (CDVA) and EPT to be similar in FLACS and 

conventional surgery, while quality of life and cost-effectiveness outcomes were not reported. 

The evidence for the relative benefit of FLACS was limited by reliance on small to moderatelysized prospective cohort studies, nearly all of which had stated financial conflicts of interest. 

Adverse events unique to FLACS involved difficulties in laser docking or patient suitability 

for the procedure. Many patients were excluded from the FSL treatment groups for orbital, 

corneal, cataract density, or medical co-morbidities. Comparative adverse events in FLACS and 

conventional surgery were found to be similar for IOL positioning, corneal thickness, macular 

edema and residual refractive error. A few studies reported mixed results of the effect of surgical 

experience on the incidence of FLACS adverse events.
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Summary of the evidence table on the effects of femtosecond laser assisted 

cataract surgery

Outcome

For each study design:

Number of studies 

(combined sample size)

Findings Strength of 

Evidence Comments

Visual acuity 2 RCTs (N=189)

4 NRCS (N=306)

No significant 

differences Low 

No differences in visual acuity outcomes 

found in either of the randomized 

trials. Unclear risk of bias for trials, low 

consistency, coherence and applicability 

of estimated effects across studies, small 

to medium sample sizes and conflicts of 

interest lower the strength of evidence.

Effective 

phacoemulsification time

1 RCT (N=76)

4 NRCS (N=615)

1 NCS (N=160)

Mixed findings Low

Trial found no significant reduction in 

EPT for FSL group. Two of the large 

nonrandomized studies (N=550) reported 

significant reductions in favor of FLACS. 

Remaining three studies found no significant 

differences. Unclear risk of bias for trial, low 

consistency, coherence and applicability 

of estimated effects across studies and 

conflicts of interest lower the strength of 

evidence.

Quality of life None None No evidence None of the included studies reported on 

quality of life outcomes. 

Intraoperative 

complications*

3 NRCS (N=1,900)

3 NCS (N=285)

Higher IOP 

for FLACS; 

Few additional 

complications 

for FLACS 

Moderate to 

Low

Low incidence of complications with FLACS, 

though increases in IOP reported across 

studies. Low applicability of estimated 

effects lowers the strength of evidence. 

Postoperative 

complications**

1 RCT (N=76)

1 NRCS (N=150)

1 NCS (N=160)

Mixed findings Low

Trial found no significant differences and 

medium-sized cohort study (N=150) found 

significantly reduced endothelial loss for the 

FLACS group. Unclear risk of bias for trial, 

low consistency and coherence of estimated 

effects across studies, small to medium 

sample sizes and conflicts of interest lower 

the strength of evidence.

Costs None None No evidence

None of the included studies reported on 

costs of FLACS compared to conventional 

cataract surgery.

Abbreviations: RCT = randomized controlled trial; NRCS = non-randomized comparative studies; NCS = non-comparative 

studies; FLACS = femtosecond laser assisted cataract surgery; EPT = effective phacoemulsification time; IOP = intraocular 

pressure

*Intraoperative complications include: capsular blockage, capsular tear, dislocated nucleus, docking failure

**Postoperative complications include: infection, retinal swelling/cystoid macular edema, intraocular decentration, corneal edema
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EVIDENCE REPORT

BACKGROUND

The preferred method of removing cataracts in the developed world is phacoemulsification.1

Using this technique, ultrasonic energy softens the dense lens material of the cataract, which 

is then extracted from the eye with suction and irrigation. Current practice includes creating 

manual corneal incisions and anterior capsulotomies, followed by phacoemulsification.2

 Recently 

these three manual procedures have been performed in an automated fashion with the use of 

the femtosecond laser (FSL). Several FSL systems have been approved by the FDA for use in 

the U.S. for some or all of these procedural steps in cataract surgery. FSL technology has been 

widely used in various refractive surgery applications in recent years.3

 Studies have suggested 

decreased phacoemulsification energy use with FSL cataract surgery4

 and have examined the 

potential advantages of more precise corneal incisions5

 and capsulotomy formation.6

Cataract surgery is a frequently performed operation in the VHA,7

 with more than 49,000 

performed in 2012. As a result, the VHA National Surgery Office has been tasked with making 

a recommendation regarding whether femtosecond lasers provide appropriate cost-benefit and 

risk-benefit ratios to support implementation for cataract surgery in the VA. Thus, an unbiased 

evidence review examining the potential benefits and adverse effects related to femtosecond laser 

assisted cataract surgery (FLACS) will aid VA leadership in determining policy for use of this 

technology. The purpose of this report is to systematically present the evidence regarding the 

effectiveness and safety of FLACS relative to conventional cataract surgery. Key questions were 

developed in conjunction with the stakeholders which address the effectiveness, safety, adverse 

consequences and economic implications of adopting FLACS into the VA system.
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METHODS

TOPIC DEVELOPMENT

The following key questions guiding this systematic review were developed after a topic 

refinement process that included a preliminary review of published peer-reviewed literature, 

consultation with internal partners and investigators and consultation with content experts and 

key stakeholders. 

Key Question 1: What is the evidence that FLACS is associated with better patient 

outcomes than conventional cataract surgery?

Population: Adults undergoing cataract surgery. 

Considerations: femtosecond laser surgery is relatively contraindicated in patients with: 

advanced glaucoma, high anxiety, tremors, dementia, facial or ocular anatomy that precludes 

adequate LASER docking (i.e. small palpebral fissures, prominent brows, irregular corneal 

surfaces) and previous refractive surgery or corneal opacities. 

Intervention: Femtosecond laser technology is used in cataract surgery to assist or replace 

aspects of conventional cataract surgery, including corneal incisions, capsulotomy and lens 

fragmentation. Lasers at or near the point of commercial release include: Alcon LenSx 

(Alcon Laboratories, Fort Worth, TX, USA); OptiMedica Catalys (OptiMedica Corp, Santa 

Clara, CA, USA); LensAR (LensAR Inc, Winter Park, FL, USA); VICTUS (Bausch + Lomb, 

Aliso Viejo, CA, USA; and Technolas Perfect Vision GmbH, Munich, Germany); IntraLase 

FS; and iFS Laser Systems (Abbott Medical Optics, Abbott Park, IL, USA). 

Only a subset of these lasers is currently FDA approved for cataract surgery.8

 Still, this 

review is inclusive of studies concerning any femtosecond laser used for cataract surgery 

applications regardless of FDA status.

Comparators: Conventional cataract surgery, defined as small-incision, phacoemulsification 

with posterior-chamber intraocular lenses (IOL) implantation.

Outcomes: Short-term patient outcomes: visual acuity—post -operative day 1. Long-term 

patient outcomes: visual acuity—after post-operative day 1 (e.g., one week, one month, 

ninety days); quality of life measures.

Study design: Controlled studies including randomized controlled trials and non-randomized 

controlled clinical trials, as well as observational studies comparing FLACS to conventional 

cataract surgery. 

Excluded study designs: Case reports, case series and studies that do not report primary data 

such as editorials and non-systematic reviews.

Timing: Our operational definition to be used for timing of patient outcomes is as follows: 

•	 Short-term—patient outcomes on post-operative day 1 

•	 Long term—patient outcomes > after post-operative day 1 (no upper limit).
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Considerations: Standards for reporting timing of post-operative outcomes often have 

variable time-horizons. For example, potential harms such as CME or IOL decentration, may 

be reported from as early as post-operative day one or after months to years in some studies.

Setting: Any.

Key Question 2a: What are the adverse effects that have been reported for 

FLACS?

Key Question 2b: What is the risk of adverse effects from FLACS compared to the 

risk associated with conventional cataract surgery?

Population: Adults undergoing cataract surgery.

Intervention: Femtosecond laser technology is used to assist or replace steps in conventional 

cataract surgery, including corneal incisions, capsulotomy and lens fragmentation.

Comparators: Conventional cataract surgery.

Outcomes: Surgical complications (intra-operative and post-operative). 

Intra-operative: 1) capsular blockage syndrome

2) dislocated nucleus

3) capsular tear

4) docking failure 

Post-operative: 1) infection

2) retinal swelling/cystoid macular edema (CME)

3) corneal edema

4) intraocular (IOL) decentration

Study design: Controlled studies and observational study designs (cohort and case-control 

studies), case reports and case series.

Timing: Short-term—intraoperative, post-operative day 1. Long term—patient outcomes > 

after post-operative day 1 (no upper limit).

Setting: Any.

Key Question 3: What is the evidence that the experience of the surgeon is 

associated with adverse effects of FLACS?

Population: Adults undergoing cataract surgery.

Intervention: Femtosecond laser technology is used in cataract surgery to assist or replace 

aspects of conventional cataract surgery, including corneal incisions, capsulotomy and lens 

fragmentation.

Comparators: Conventional cataract surgery.

Study designs: Controlled studies and observational study designs including economic 

evaluation studies (cohort and case-control studies).
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Excluded study designs: Case reports, case series and studies that do not report primary data 

such as editorials and non-systematic reviews.

Outcomes: Surgical complications (intra-operative and post-operative). 

Intra-operative: 1) capsular blockage syndrome

2) dislocated nucleus

3) capsular tear

4) docking failure 

Post-operative: 1) infection

 2) retinal swelling/cystoid macular edema (CME)

 3) corneal edema

 4) intraocular (IOL) decentration

Timing: Short-term—patient outcomes on post-operative day 1. Long term—patient 

outcomes > after post-operative day 1 (no upper limit).

Setting: Any.

Appendix C presents these eligibility criteria for considered studies in a PICOTS (Population, 

Intervention, Comparators, Outcomes, Timing and Setting) table. Figure 1 illustrates the analytic 

framework that guided our review and synthesis.
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FLACS 

vs.

conventional 

cataract 

surgery

KQ1

Short-term Outcome:• Visual acuity post-operative at day 1Long-term Outcomes:• Visual acuity after post-operative day 1 (e.g., 1 week, 1 month or 90 days)• Quality of life

KQ3

Adverse events:

• Intra-operative complication

○ Capsular blockage syndrome○ Dislocated nucleus○ Capsular tear○ Docking failure

• Post-operative

○ Infection○ Retinal swelling/Cystoid Macular 

Edema (CME)

○ Intraocular (IOL) decentration○ Corneal edema

KQ2a, KQ2b

Context: 

Experience of 

surgeon
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SEARCH STRATEGY

Search strategies were developed in consultation with a research librarian from database 

inception to May 2013. We conducted a primary review of the literature by systematically 

searching, reviewing and analyzing the scientific evidence as it pertained to the research 

questions. To identify relevant articles, we began by searching MEDLINE®, the Cochrane library, 

ClinicalTrials.gov, premarket notification 510(k) summaries from the FDA and conference 

proceedings of societies for ophthalmology and refractive surgery. Searches were conducted 

from April 2013 to July 2013, with no limit on year of publication. 

We searched ClinicalTrials.gov to identify in-progress or unpublished studies. We searched 

conference proceedings of ophthalmologic societies and topic specific journals, including the 

following: The American Society of Cataract and Refractive Surgery; Journal of Cataract & 

Refractive Surgery; American Academy of Ophthalmology; Ophthalmology; International 

Society of Refractive Surgery; American Academy of Ophthalmic Executives; The Foundation 

of the American Academy of Ophthalmology; The Royal College of Ophthalmologists; COS 

Conference Papers Index; and Proceedings First (OCLC). Appendix A provides the search 

strategy in detail. We obtained additional articles from reference lists of pertinent studies, 

reviews, editorials and by consulting experts. All citations were imported into an electronic 

database (EndNote X1).

STUDY SELECTION

Two reviewers assessed abstracts of citations identified from literature searches for relevance. 

Full-text articles of relevant abstracts were retrieved for further review. Each article retrieved 

was independently reviewed by two reviewers using eligibility criteria (Appendix B). Included 

studies were published in the English language and involved adults undergoing cataract surgery 

using femtosecond laser technologies. 

Using pre-specified inclusion/exclusion criteria, titles and abstracts were reviewed for potential 

relevance to the key questions. At the full-text screening stage, two independent reviewers 

assessed each study. Disagreements were discussed to come to a final decision on inclusion/

exclusion. If the two independent reviewers could not come to an agreement, a third reviewer 

assessed the study in question. For all excluded studies, full-text reviewers also came to 

unanimous agreement on the reason for exclusion. Articles meeting eligibility criteria were 

included for data abstraction. 

DATA ABSTRACTION

Data from published reports were abstracted into a customized database by one investigator and 

reviewed for accuracy by a second investigator. From each study, we abstracted the following: 

study design, objectives, setting (country, institution information), population characteristics 

(including sex, age, medical comorbidities), subject eligibility and exclusion criteria, number of 

subjects, duration of follow-up, the study and comparator interventions, health outcomes, adverse 

events and number and experience of the surgeons. 
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STUDY QUALITY

We adapted the Newcastle Ottowa tool9 to assess the quality of observational studies. For 

randomized studies, we used the Cochrane Collaboration tool for assessing the risk of bias. Two 

reviewers independently assessed the quality of each study and disagreements were resolved 

through discussion. We added additional criteria as necessary to account for methodological 

issues specific to this subject area, such as financial conflicts of interest and the number of studies 

produced by a small number of authors and coauthors (i.e., same team replication). We did not 

report an overall summary assessment for observational studies because there are no validated 

criteria for doing so.10

RATING THE BODY OF EVIDENCE

We assessed the overall quality of evidence for outcomes using a method developed by the 

GRADE Working Group.11 We present the summary of evidence in Table 3. The GRADE 

method considers the consistency, coherence and applicability of a body of evidence, as well as 

the internal validity of individual studies, to classify the grade of evidence across outcomes as 

follows: 

•	 High = Further research is very unlikely to change our confidence on the estimate of 

effect.

•	 Moderate = Further research is likely to have an important impact on our confidence in 

the estimate of effect and may change the estimate.

•	 Low = Further research is very likely to have an important impact on our confidence in 

the estimate of effect and is likely to change the estimate.

•	 Very Low = Any estimate of effect is very uncertain.

DATA SYNTHESIS

We summarized the primary literature by abstracting relevant data, developing data tables and 

qualitatively synthesizing the literature for each key question. We determined the feasibility of 

completing a quantitative synthesis (i.e., meta-analysis) to estimate summary effects depending 

on the volume of relevant literature, conceptual homogeneity of the studies and completeness of 

results reporting. We conducted meta-analyses of commonly reported outcomes, following the 

MOOSE guidelines for conducting meta-analyses of observational studies.12

 All analyses were 

conducted using StataIC 11 (StataCorp, College Station, Texas). We assessed the presence of 

statistical heterogeneity among the studies by using standard chi-square tests and the magnitude 

of heterogeneity by using the I

2

 statistic.13 We explored models using both mean and ratio of 

means based on a random effects model. However, because of concerns of heterogeneity among 

studies we do not report the combined estimates and instead present forest plots as a visual aid to 

illustrate individual study results. 
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RESULTS

LITERATURE FLOW

We reviewed 468 titles and abstracts from the electronic search and identified 436 additional 

references through manual searching of reference lists, input from technical advisors and 

reviewing conference proceedings of ophthamalogic societies for recent unpublished or ongoing 

studies. 

After applying inclusion/exclusion criteria at the abstract level, seventy full-text articles were 

reviewed, as shown in Figure 2. Of the full-text articles, we rejected fifty-four that did not meet 

our inclusion criteria.
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Figure 2: Femtosecond laser assisted cataract surgery – literature flow diagram

436 citations identified fro conference proceedings of societies, 

reference lists of review articles, and manual searches for 

recent, unpublished or ongoing studies.

904 citations compiled for review of titles and abstracts.

834 titles and abstracts excluded for 

lack of relevance.

70 potentially relevant articles or ongoing research abstracts retrieved for further review.

34 excluded articles:

	 Not relevant to key questions = 7

	 Intervention not in scope = 1

	 Studied outcomes not in scope = 2

	 Excluded study design or study 

contains no primary data = 6

	 Retained for background, 

discussion, methods or other 

contextual purposes = 18

15 published studies addressing one or 

more key questions:

9 studies reporting the benefits 

of FLACS compared with 

conventional cataract surgery 

(KQ1).

9 studies reporting the unique 

risks of FLACS (KQ2a) 

or risks compared to 

conventional cataract surgery 

(KQ2b).

19 abstracts of unpublished, recent or 

ongoing studies.

2 studies addressing intra-/postoperative risks with regard to 

the experience of the surgeon 

(KQ3).

468 published articles identified from electronic searches of databases and specific journals:

	 76 from MEDLINE® on 05/08/2013

	 3 from the Cochrane library (Central Register of Controlled Trials and Database of Systematic 

Reviews) on 03/18/2013

	 14 from Clinicaltrials.gov on 04/07/2013

	 6 premarket notification 510(k) summaries from the FDA on 05/09/2013

	 369 from journals specific to ophthalmology or cataract surgery on 05/08/2013
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KEY QUESTION 1: What is the evidence that FLACS is associated with 

better patient outcomes than conventional cataract surgery?

Summary of findings 

We identified nine studies addressing the comparative effectiveness of FLACS versus 

conventional surgery, including three small to medium-sized randomized controlled trials. Six of 

these studies (and all three of the randomized controlled trials) were conducted at Semmelweis 

University, Budapest, Hungary, all surgeries having been performed by the same surgeon, using 

the Alcon LenSx laser. Two studies were conducted in an ophthalmology group practice, at 

Launceton Eye Hospital, Tasmania, Australia, using the OptiMedica Catalys laser. Sample sizes 

in these studies ranged from 25 to 400 patients, with follow-up periods extending from two 

weeks to one year. 

The most commonly reported relevant outcomes in these comparative studies were: postoperative corrected distance visual acuity (CDVA); and, effective phacoemulsification time 

(EPT). We conducted a meta-analysis of CDVA and EPT, but heterogeneity precluded calculation 

of a reliable summary effect estimate. The results of individual studies are presented in 

Figures 3 and 4. Overall, there was low evidence of comparative benefit of FLACS from three 

randomized controlled trials and six observational studies. There were no significant differences 

noted between groups for CDVA outcomes. EPT outcomes were mixed, with results either 

comparable between FSL and conventional cataract surgery groups or favoring FSL groups. No 

studies addressed quality of life measures. Methodological concerns were noted regarding the 

generalizability of studies conducted from limited sites and potential sample selection bias from 

enrollment into FSL and conventional surgery groups.

Detailed findings 

Table 1 shows the detailed characteristics and findings of the included comparative studies. 

A randomized trial (N=134) with 77 patients in the FSL group and 57 patients in the 

conventional cataract surgery group utilized the Alcon LenSx laser.14 Baseline age between 

groups was similar, with cataract density not reported. Reported post-operative CDVA at twelve 

weeks was 0.93±0.87 in the FSL group and 0.95±0.91 in the conventional group (p>0.05). 

Another randomized trial (N=45) compared a FSL group (n=25) versus a conventional group 

(n=20) using the Alcon LenSx laser.15 At one year, post-operative CDVA was measured as 

.97±.06 for the FSL group versus .92±.09 for the conventional group (p=.03).

One study (n=400) enrolled consecutive patients electing for FSL (n=200). Patients who did 

not elect FSL underwent conventional phacoemulsification cataract surgery (n=200) and were 

considered the control group.4 Five surgeons participated in this study, for which the OptiMedica 

Catalys laser was used in the FSL arm. Both groups were statistically similar at baseline in age 

and cataract density. EPT was reported as significantly decreased in the FSL group (4.3 vs 14.3 

seconds; p<0.001). 

Another study by the same author (N=201) was a case-control design, with a single surgeon using 

the OptiMedica Catalys laser in the FSL cases (n=150), compared to conventional cataract surgery 

controls (n=51).16 Baseline demographics and cataract density were similar statistically between 
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groups. CDVA outcomes at three weeks post-operatively measured 0.67 in both groups (p>0.05). 

EPT was significantly decreased in the FSL group (2.33±2.28 vs 14.24±10.90 seconds; p<0.0001).

Another study (N=91) compared FSL groups (n=48) with conventional surgery groups (n=43), 

using the Alcon LenSx laser.17

 Baseline age and gender distribution was similar between groups 

but cataract density was not reported. At six months, post-operative CDVA was reported as as 

.97±.08 in the FSL group and .97±.06 in the conventional group (p>.05).

One study (N=76) enrolled equal groups (n=38) of FSL and conventional surgery patients, 

using the AlconLenSx laser.18 Demographic characteristics and cataract density at baseline were 

reported as being similar between the groups. The study excluded patients with denser cataracts, 

low cooperation and FSL procedure contraindications such as corneal scarring. EPT was reported 

as 0.10±0.12 for the FSL group and 0.12±0.13 seconds for the conventional group (p>0.05). 

Another study (N=40) enrolled patients into FSL (n=20) and conventional groups (n=20) using 

the Alcon LenSx laser.19

 Outcomes reported which compared FSL and conventional surgery 

groups were EPT (0.08 for FSL vs 0.08 for conventional; p=0.94) and one month post-operative 

CDVA (0.83±.0.65 for FSL vs 0.95±0.87 for conventional; p-value not reported).

A final study (N=25) enrolled patients in FSL (n=12) and conventional surgery (n=13) groups with 

similar baseline demographic characteristics, with cataract density not reported.20

 EPT was reported 

as not statistically different between groups. Eight week post-operative CDVA was measured as 

1.0±0.0 for the FSL group and .95±.08 for the conventional group (p-value not reported).

Meta-analyses of CDVA and EPT

Figures 3 and 4 present plots of meta-analyses conducted on CDVA and EPT outcomes. 

Relatively few studies reported these outcomes in a consistent and combinable manner. We 

identified four studies for the meta-analysis of CDVA16,17,19,20 and four studies for the metaanalysis of EPT.4,16,18,19 Given the moderate to substantial heterogeneity among studies (for CDVA 

I-squared=63.9%, p = 0.040; for EPT I-squared=94.1%, p = 0.000), a summary estimate of the 

effect is unreliable. Instead, we present the forest plots as visual aids to illustrate individual study 

results. 

The scales for CDVA used across studies were consistent when converted to decimal units, 

therefore we used mean difference to combine study results. We found moderate heterogeneity 

among studies. Consequently, we conducted a sensitivity analysis by excluding a presumed 

outlying study.19 We found that this exclusion did not alleviate concerns with heterogeneity, 

nor did it change the substantive findings of the meta-analytic results. As a result, we included 

all four studies in the meta-analyses, represented in Figure 3 which illustrates no significant 

difference in CDVA for patients undergoing FSL or conventional procedures. 

For EPT, we used the ratio of the mean to reduce the variation among studies and estimated the 

relative difference in EPT. Despite these efforts, there was still significant heterogeneity among 

studies. We would have included one additional study in the meta-analysis,20

 but this study did 

not report a point estimate for EPT and could not be included. Figure 4 shows what appears to be 

a reduction of mean EPT in the FLACS group, compared to the conventional group. However, 

since the 95% confidence interval includes one, this difference is not significant. 
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Figure 3: Corrected distance visual acuity (CDVA) in studies comparing femtosecond laser with 

conventional cataract surgery

17

FIGURE 3: CORRECTED DISTANCE VISUAL ACUITY (CDVA) IN 

STUDIES COMPARING FEMTOSECOND LASER WITH

CONVENTIONAL CATARACT SURGERY

Overall (I-squared = 63.9%, p = 0.040)

Study

Nagy, 2012

Mihaltz, 2011

Ecsedy, 2011

Abell, 2013

0.05 (0.01, 0.09)

0.00 (-0.03, 0.03)

Weighted 

mean 

difference

-0.12 (-0.25, 0.00)

0.00 (-0.03, 0.03)

12, 1 (.004)

43, .97 (.08)

20, .832 (.27)

150, .67 (.118)

N, mean (SD)

13, .95 (.08)

51, .97 (.06)

Control

20, .955 (.0978)

51, .67 (.0793)

%

26.03

33.66

Weight

6.52

33.79

0.05 (0.01, 0.09)

0.00 (-0.03, 0.03)

(95% CI)

-0.12 (-0.25, 0.00)

0.00 (-0.03, 0.03)

N, mean (SD)

12, 1 (.004)

43, .97 (.08)

Treatment

20, .832 (.27)

150, .67 (.118)

-.3 -.15 0 .15

←Favors conventional surgery Favors FLACS→

Figure 4: Effective phacoemulsification time (EPT) in studies comparing femtosecond laser with 

conventional cataract surgery

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Laser Assisted Cataract Surgery

FIGURE 4: EFFECTIVE PHACOEMULSIFICATION TIME (EPT) IN 

STUDIES COMPARING FEMTOSECOND LASER WITH

CONVENTIONAL CATARACT SURGERY

PL Overall (I-squared = 94.1%, p = 0.000)

Study

Takacs, 2012

Abell, 2013

Ecsedy, 2011

Abell, 2012

0.83 (0.50, 1.39)

0.16 (0.13, 0.21)

1.00 (0.54, 1.84)

0.30 (0.24, 0.37)

24.02

26.38

22.90

26.69

Ratio of

0.83 (0.50, 1.39)

0.16 (0.13, 0.21)

1.00 (0.54, 1.84)

Means (95% CI)

0.30 (0.24, 0.37)

%

24.02

26.38

22.90

Weight

26.69

.125 .25 .5 1 2

←Favors FLACS Favors conventional surgery → 
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KEY QUESTION 2A: What are the adverse effects that have been 

reported for FLACS? 

Summary of findings

Seven studies were identified addressing adverse effects unique to FLACS. Sample sizes in these 

studies ranged from 25 to 1300 patients, with follow-up periods extending from immediately 

following the procedure to three months post-operative. 

We grouped the adverse event outcomes in these studies by either: 1) those occurring as a 

result of difficulties with the laser-patient interface; or, 2) the change in intraocular pressure 

(IOP) measured during the FLACS procedure. Five studies reported difficulties related to the 

laser interface with the ocular surface (including the orbital structures). Two studies measured 

intraocular pressure (IOP) fluctuation during FLACS procedures. A small proportion of patients 

experienced suction breaks, second docking attempts and aborted procedure adverse events. 

FSL application is also associated with an increase in IOP. Overall, we found moderate to low 

strength of evidence for adverse events with methodological concerns from enrollment criteria 

used for FSL surgery groups.

Detailed findings 

Laser interface events 

One study compared EPT in two groups of patients (n=80 per group) undergoing FLACS with 

two different laser grid-sizes.21 In both groups, using the OptiMedica Catalys FSL, a total of 

twelve patients required a second docking attempt. No other intra-operative or subsequent 

adverse events were noted in either group after four weeks of follow-up.

A case series study (N=100) of IOP measurements during FLACS noted no patients had suction 

loss during FSL (Catalys) treatment.22 No adverse events were reported at the one hour postoperative timepoint.

A comparative safety and effectiveness study of 400 patients (n=200 per group), reported four 

patients in the FSL (Catalys) group, for whom the laser procedure was aborted.4 One patient 

was claustrophobic, one with kyphosis made postioning unsafe and two patients had excessive 

movement during the procedure. 

A case series of the initial 200 patients undergoing FLACS (Alcon LenSx) in a single group 

practice reported intraoperative complications of this cohort.23 Mean docking attempts were 

reported as 1.5 per eye. Five eyes had suction breaks during the FSL procedure, with no adverse 

events noted with the manual completion of the surgeries. A continuation study of this same group’s 

experience, using the same FSL platform, reported intraoperative complications of FLACS for a 

subsequent series of 1300 patients.24 No additional adverse effects unique to FLACS were noted, 

though data related to surgical experience was reported (see findings for Key Question 3).

Intraocular pressure events

The interface of any of the FSL platforms with the optical surface causes an increase in 

intraocular pressure (IOP).8

 This occurs due to applanation and/or suction applied during FSL 
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docking and laser application. This laser-patient interface must be stable throughout the phases of 

imaging, capsulotomy, corneal incisions and photodisruptive pre-fragmentation of the cataract. 

The various FSL platforms use different docking mechanisms, which can affect the degree to 

which the IOP increases during the FLACS procedure.1

 Both of the IOP studies included in this 

review utilized the OptiMedica Catalys FSL. 

One case series (N=100) recorded IOP at two time-points—during and one hour following 

the FLACS procedure.22 Mean IOP increased to 27.6 ±5.5 mmHg in this cohort. Patients were 

queried post-operatively and none reported experiencing amaurosis (blindness), during FLACS. 

An additional case series study to analyze IOP during FLACS (N=25), reported measurements 

at baseline and at various time-points.25 Mean baseline IOP (17.4±2.4 mmHg), increased to 

36.0±4.4 mmHg during FSL application. This represented a mean increase from baseline of 

18.5±4.7 mmHg. 

KEY QUESTION 2B: What is the risk of adverse effects from FLACS 

compared to the risk associated with conventional cataract surgery? 

Summary of findings

Nine studies addressed the adverse effects of FLACS compared to conventional cataract surgery. 

Sample sizes in these studies ranged from 25 to 400 patients, with follow-up periods extending 

from one week to one year. 

We grouped the adverse event outcomes of these studies by the ocular structures which were 

affected. Five of these studies reported, variously: capsulotomy configuration, position and the 

resultant effects on IOL decentration and refractive outcomes. Two of these studies reported 

post-operative corneal edema by measuring either corneal thickness or corneal endothelial cell 

loss. An additional two studies compared post-operative macular thickness and morphology, as 

measured by optical coherence tomography (OCT). The FSL and control groups were similar 

for post-operative corneal thickness and macular edema measurements, with corneal endothelial 

cell loss decreased in the FSL group in one study. Overall, we found moderate to low strength of 

evidence for comparative adverse events with methodological concerns from enrollment criteria 

used for the FSL and conventional surgery groups.

Detailed findings

Capsulotomy sequelae

Five comparative studies of capsulotomy characteristics reported multiple aberrometry and 

geometric measurement outcomes.6,14,15,17,26 However, none of the prioritized adverse events were 

reported in any of these studies (see Appendix C). 

Corneal morphology and function

One study (n=76) compared central corneal thickness by pachymetry measurement at one month 

post-operatively in equal numbers of patients. At enrollment, patients with dense cataracts 

were excluded from participation in the study.18 These authors reported no statistical difference 
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between corneal thickness between FSL vs. conventional groups (545±31μm vs. 557±42 μm; 

p>.05) Another study reported decreased corneal endothelial cell loss in the FSL group (n=150) 

vs. the control group (n=51) at three weeks post-operatively (-143.8±208.3 vs -224±188.95; 

p=0.02).16

Macular morphology

Two studies compared macular thickness between FSL and conventional surgery groups via 

OCT measurements. One of these studies (n=25) noted no statistically significant differences in 

macular thickness between groups in all but one retinal layer post-operatively at eight weeks.20

Here, the outer nuclear layer was thicker in the control group (96.5±10.46μm vs 87.54±10.31μm; 

p=.04). Another study (n=40) measured macular thickness post-operatively at one month, 

reporting no significant differences between groups in macular total volume, foveal or outer 

macular ring thickness.19

KEY QUESTION 3: What is the evidence that the experience of the 

surgeon is associated with adverse effects of FLACS?

Summary of findings

Three studies reported outcomes relevant to the experience of the surgeon in performing 

the FLACS procedure. Sample sizes in these studies ranged from 200 to 1300 patients, with 

follow-up periods extending from two weeks to three months. Overall, one of the studies found 

no significant differences between outcomes for initial and subsequent groups of patients 

undergoing FLACS, while on the other hand two studies from the same team of researchers 

found significantly fewer complications associated with greater experience with FLACS. 

There were methodological concerns from enrollment criteria used for the FSL and conventional 

surgery groups.

Detailed findings

One study compared the safety and effectiveness of FSL to conventional surgery in 200 

consecutive patients who elected FSL or conventional surgery procedures.4 Further sub-analysis 

of the FSL group into initial (n=100) and subsequent (n=100) patients reported outcomes for 

EPT and docking attempts. No statistically significant differences were noted between initial 

and subsequent groups for either of these FSL parameters (mean EPT: 3.52±4.18 for FSL vs. 

4.75±5.22 for conventional group; p=0.0674; mean docking attempts: 1.49±0.64 for FSL vs. 

1.36±0.79 for conventional group; p=0.2025).

Another study compared intraoperative complications in four groups of consecutive patients 

undergoing FLACS (n=50 in each group) who were followed for three months.23

 The number 

of mean docking attempts was greater in the initial 100 patients than in the subsequent 100 

patients (1.85 for FSL vs 1.2 for conventional group; p<0.05). The seven surgeons participating 

in this study were all from a single group practice. Three of these surgeons had prior “extensive” 

experience with the FSL in LASIK surgery. The study noted these “refractive surgeons” had 

statistically fewer complications than did the “non-refractive surgeons” in their first 100 cases. 
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No significant difference in complications between these surgeon groups was noted after these 

initial 100 cases. 

An extension of the above study23 reported complication rates in a subsequent consecutive 

patient group (n=1300) treated with FLACS by the same surgical group practice, compared 

to the initial group of 200 patients.24 Patients were followed for three months. Complications 

were significantly decreased in the subsequent group for docking attempts (1.5 for FSL vs 

1.05 for conventional group), anterior capsular tears (4% for FSL vs 0.31% for conventional 

group), posterior capsular tears (3.5% for FSL vs 0.31% for conventional group) and posterior 

lens dislocation (2% for FSL vs 0% for conventional group). The reported p-values for all 

comparisons were p<0.001.

ONGOING STUDIES

We reviewed recent conference proceedings from ophthalmologic societies for topic relevance. 

We coded conference abstracts that potentially address one or more of our key questions and 

describe the study characteristics in Table 2.
22

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ndings of studies of femtosecond laser assisted cataract surgery

Study Design;

Number of Patients; Length 

of Follow-up; Laser Used

Mean age; % male; cataract 

density (LOC III score) KQ 1: Benefits KQ 2: Adverse events KQ 3: Surgeon experience

Prospective cohort study of two FLACS techniques—no conventional surgery comparator (single surgeon)N=160 patients 4 weeks OptiMedica Catalys

Tx group 1 (350 grid):71±12; 32%; 3.7±08Tx group 2 (500 grid):72±11; 60%; 3.5±08

EPT:Tx group 1=.03±.05 secondsTx group 2=.21±.26 seconds p-value=NR

Intraoperative:-Free-floating anterior capsule noted in all eyes-12 2nd docking attempts

Post operative:None noted

NA

Case series (2 surgeons)N=100 patients1 hour OptiMedica Catalys

70±12; 51%; NR NA Intraoperative:

27.6±5.5mmHg increase in mean IOP

NA

Prospective cohort study of FLACS and conventional surgery (single surgeon)N=91 patients6 months Alcon LenSx

Tx group:75.0; 21%; NRC group:70.7; 18%; NR

CDVA:Tx group=.97±.08C group= .97±.06 p>.05

NR NA

Prospective cohort study of FLACS and conventional surgery (single surgeon)N=25 patients8 weeks Alcon LenSx

Tx group:55.17±17.25; 58.3%; NRC group:62.00±14.27; 38.5%; NR

CDVA:Tx group= 1.0±0.0C group= .95±.08 p-value=NREPT:Differences between Tx and C were NS

None noted NA
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Study Design;

Number of Patients; Length 

of Follow-up; Laser Used

Mean age; % male; cataract 

density (LOC III score) KQ 1: Benefits KQ 2: Adverse events KQ 3: Surgeon experience

Randomized trial of FLACS and conventional surgery (single surgeon)N=111 patients1 week Alcon LenSx

Tx group:65±13; 27.8%; NRC group:68±15; 29.8%; NR

NA NR NA

Randomized trial of FLACS and conventional surgery (single surgeon)N=45 patients1 year Alcon LenSx

Tx group:63.55±13.65; 25%; NRC group:68.24±10.77; 8%; NR

CDVA:Tx group=0.97±.06C group= 0.92±.09 p=.03

NR NA

Prospective cohort study of FLACS and conventional surgery (single surgeon)N=40 patients1 yearAlcon LenSx

Tx group:63.78±13.97; 25%; NRC group:71.60±1.34; 30%; NR

NA NR NA

Prospective cohort study of FLACS and conventional surgery (single surgeon)N=76 patients1 monthAlcon LenSx 

Tx group:65.18±12.42; 26.3%; 2.32±.97C group:66.93±10.99; 39.5%; Schiempflug nuclear density 2.13±1.22

EPT:Tx group=0.10±0.12sC group= 0.12±0.13s p>.05

Postoperative:Central corneal thickness Tx group=545±31 μmC group= 557±42 μmp>.05

NA

Randomized trial of FLACS and conventional surgery (single surgeon)N=134 patients12 weeksAlcon LenSx

Tx group:65.18±12.6; NR; NRC group:64.37±12.37; NR; NR 

CDVA:Tx group=0.93±0.87C group= 0.95±0.91 p>.05 

NR NA
24

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Study Design;

Number of Patients; Length 

of Follow-up; Laser Used

Mean age; % male; cataract 

density (LOC III score) KQ 1: Benefits KQ 2: Adverse events KQ 3: Surgeon experience

Prospective cohort of FLACS and conventional surgery (single surgeon)N=40 patients1 monthAlcon LenSx

Tx group:64 (median); 40%; NRC group:66 (median); 25%; NR

CDVA (median):Tx group=0.83±0.65 C group= 0.95±0.87 EPT (median, IQR):Tx group=0.08s (0.03-0.12)C group= 0.08s (0.03-0.15) p=0.94

NA NA

Parallel cohort study of FLACS and conventional surgery (5 surgeons)N=400 patients2-3 weeksOptiMedica Catalys

Tx group:73.3±9.9; 48%; 2.81±.82 (Pentacam Nuclear Staging) C group:71.8±10.8; 42%; 2.71±0.72 (Pentacam Nuclear Staging)

EPT:Tx group=4.3 secC group= 14.3 sec p<0.0001

Intraoperative:Reported for the Tx group,Imperfect capsulotomy= 0.5%Focal adhesions= 2%Reduction of pupil size= 3%Capsular rupture= 0.5% Aborted (claustrophobia), n=1 Aborted (unsafe postioning), n=1Aborted (patient movement), n=2 Reported for C group:No adverse events noted

EPT:1st 100 cases=3.52+-4.18 

secs 2nd 100 cases=4.75+-5.22 

secs;P=0.0674

Case control study of FLACS and conventional surgery (single surgeon)N=150 patients3 weeksOptiMedica Catalys

Tx group:72.8±10.5; 46%;2.59±0.71 (Pentacam Nuclear Staging)C group:71.8±10.8; 45.1%; 2.52±0.72 (Pentacam Nuclear Staging)p>0.05

CDVA:Tx group=0.67C group= 0.67 p>0.05EPT:Tx group=2.33±2.28s C group=14.24±10.90 sp<0.0001

Postoperative:Endothelial lossTx group= -143.8±208.3C group= -224±188.95 p=0.022

NA

Prospective non-comparative cohort study N=25 patientsimmediate postopOptiMedica Catalys

72.5±7.7; 40%; NR NA Intraoperative:

Mean baseline IOP=17.5±2.4mmHg Vacuum On IOP=28.9±3.2mmHg FSL application=36.0±4.4 mmHg p<0.001 (1-way ANOVA compared to baseline)

NA
25

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Study Design;

Number of Patients; Length 

of Follow-up; Laser Used

Mean age; % male; cataract 

density (LOC III score) KQ 1: Benefits KQ 2: Adverse events KQ 3: Surgeon experience

Prospective non-comparative cohort study (7 surgeons)N=1500 patients (N=200 initial, N=1300 subsequent)3 monthsAlcon LenSx

Initial Tx group:69±9.8; NR; NRSubseqent Tx group:70.1±10.6; NR; NR

NA Intraoperative*:

-mean docking attempts=1.5-suction breaks=5 eyes-small anterior capsule tags=10.5%-posterior capsular rupture=3.5%(*These findings pertain to the initial study of N=200 patients)

Complications with increasing surgeon experience (docking attempts; anterior capsular tears; post capsular tears; IOL dislocation)*:1st 200 cases= 1.5; 4%; 

3.5%; 2% 2nd 1300 cases= 1.05; 

0.31%; 0.31%; 0%p<0.001 for all comparisons(*These findings pertain to the initial and subsequent study of N=1500 patients)

ct surgery group; Tx = femtosecond laser cataract surgery treatment group; N = number of subjects; LOC III score = lens opacities classification system III 

mulsification time; IOP = intraocular pressure; CDVA=corrected distance visual acuity; UDVA=uncorrected distance visual acuity; BDVA=best distance visual 

NR = not reported; NA = not applicable; NS = not statistically significant; FU = follow-up; FSL=femtosecond laser; FLACS=femtosecond laser-assisted cataract 
26

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oming studies presented at recent conference proceedings or registered on ClinicalTrials.gov

stract Title Conference, Location, Year Population; Study Design; Setting Study Objectives

ation of Circularity and 

second Laser Versus 

apsulotomy in Singapore 

re (1118)

ClinicalTrials.govOnline only

N≈22Prospective, randomized studySingapore National Eye Centre, Singapore

Evaluate the circularity of the anterior capsulotomy performed by FLACS versus conventional cataract surgery.

mes of First 100 Cases 

aser–Assisted Cataract 

mic Institution in 

ASCRS Paper. San Francisco, CA. 2013

 N=100 eyesProspective cohort studySingapore

Examine safety and visual outcomes of FLACS versus control cases.

Healing Patterns 

cond Laser–Assisted 

ASCRS Paper,San Francisco, CA. 2013

N=24 patientsProspective randomized studyNR

To evaluate size and shape of femtosecond laser anterior capsulotomy during 4 week healing.

e Predictability of Manual 

nd Laser Capsulotomy 

y With Multifocal IOL 

ASCRS Paper. San Francisco, CA. 2013

N=50 patientsNRNR

To compare refractive predictability of multifocal IOL performance with manual versus laser refractive capsulotomy.

e With Femtosecond 

taract Surgery

ASCRS Paper. San Francisco, CA. 2013

N=5 patientsNRNR

Femtosecond laser technology use in cataract surgery has several differences that can cause complications: 1) the anterior capsule is open prior to opening the eye therefore an anterior chamber collapse can result in anterior capsule tears, 2) large gas bubbles posterior to the lens can contribute to capsular block syndrome, 3) an incomplete capsulorrhexis can result in radial extension and 4) laser energy in the nucleus can be directed too anterior, too peripheral and too posterior. Adjustments to the surgical technique can help manage these complications appropriately.

sions and Arcuate 

FemtoSecond Laser 

aract Surgery

ClinicalTrials.govOnline only

N=29 patientsNon-Randomized trialLoden Vision Centers, Tennessee, USA

The purpose of this study is to prove the efficacy and safety of the Femtosecond laser to create a clear corneal incision during cataract surgery.

nventional and 

er-Assisted 

n Cataract Surgery on 

ASCRS Paper. San Francisco, CA. 2013

N=20 patients (N=20 eyes)NRNR

To compare the effect of conventional and femtolaser assisted (LensX) phacoemulsification cataract surgery on the macula, using optical coherence tomography (OCT).

le Center Clinical Study 

sing the LenSx 550 

ClinicalTrials.govOnline only

N=60Prospective Single Center Trial Semmelweis University, Hungary

The objective of this study is to evaluate the ability of the LenSx 550 laser to successfully perform anterior capsulotomy during cataract surgery.
27

ond Laser Assisted Cataract Surgery Evidence-based Synthesis Program

9CONTENTS 34

stract Title Conference, Location, Year Population; Study Design; Setting Study Objectives

rgery With the 

er Technology

ClinicalTrials.govOnline only

N=10Non-Randomized trialLoden Vision Centers, Tennessee, USA

The purpose of this study is to prove the efficacy and safety of the Femtosecond laser to create a clear corneal incision during cataract surgery.

ulative Disbursement of 

osecond Laser Cataract

ASCRS Paper. San Francisco, CA. 2013

N=151 eyesNRNR

Pretreatment with the Catalys femtosecond laser for cataract surgery allows for a greater than fifty percent reduction in ultrasound power during cataract extraction with the Infiniti phacoemulsification system with Ozil. This reduction in power may lead to quiter eyes with less edema and inflammation and a quicker visual recovery in the early postoperative period for femtosecond pretreatment group compared to a phacoemulsification group.

mtosecond Laser and 

my on Postoperative 

ASCRS Poster. 2011 N=99 eyes

NRNR

 To compare postoperative quality of vision outcomes from capsulotomies created using a femto-second laser with those using manual continuous curvilinear capsulorrhexis (CCC). 

f the Crystalline Lens ClinicalTrials.gov

Online only

N=75A Prospective Single-Center TrialMexico

The objective of this study is to evaluate the feasibility of the LensAR laser system to surgically intervene within the crystalline lens. The primary goal of this initial study is to establish safety parameters as compared with conventional phacoemulsification procedures and to evaluate the ability to provide an accurate and consistent anterior capsular opening (capsulotomy).

 and Incidence of Dry 

e Cataract Extraction 

d Laser

ClinicalTrials.govOnline only

N=40Prospective cohort studyOphthalmic Consultants of Long Island – Rockville Centre. USA

The study objective is to assess changes in corneal sensation and dry eye signs and symptoms following cataract extraction/femtosecond arcuate relaxing incisions. Our clinical hypothesis is to determine if a combination of cataract surgery and femtosecond arcuate relaxing incisions lead to a reduction in corneal sensation and the onset or worsening of dry eye signs and symptoms.

perience Performing 

with and without 

er

eding)

ARVO Poster Session, 2013

N=44 eyes Observational studyUniversity of Illinois, USA

To document and compare the resident experience performing cataract surgery with femtosecond laser with standard cataract surgery performed without femtosecond laser.

ly corneal peripherial 

s following femtosecond 

taract surgery and 

oemulsification

eding)

ARVO Poster Session, 2013

N=15 patients (N=15 eyes)Observational studySemmelweis University, Hungary

To compare early corneal peripherial endothelial cell loss after femtosecond laser – assisted cataract surgery and conventional phacoemulsification, using non-contact specular microscopy.

er Pretreatment to 

Surgery in Brunescent 

ASCRS Poster. 2012 Eye n=68

NRNR

To evaluate ease of removal of laser‐fragmented cataracts. 
28

ond Laser Assisted Cataract Surgery Evidence-based Synthesis Program

9CONTENTS 34

stract Title Conference, Location, Year Population; Study Design; Setting Study Objectives

se of Adoption of 

aract Surgery

ASCRS PosterSan Francisco,CA 2013

NRNRNR

Examine the ease of use, compatibility of the system and quality of outcomes with femtosecond laser-assisted cataract surgery.

neal Oedema and 

ss After Femtosecond 

t Compared With 

ract Surgery

ASCRS Paper. San Francisco, CA. 2013

Patient n=140 Prospective case-control studyNR

Femtosecond laser pretreatment followed by phacoemulsification cataract surgery is associated with a significant reduction in postoperative oedema and endothelial cell loss compared to conventional phacoemulsification.

osecond Laser Cataract 

dardized Surgical 

ASCRS PosterSan Francisco,CA 2013

N=180 eyes Prospective, non-randomized, multi-center study NR

The use of standardized surgical planning in femtosecond laser cataract surgery provided uncomplicated surgical planning with reproducible excellent outcomes.

ety of Cataract and Refractive Surgery; ASCRS♦ASO= A Symposium and Congress; ARVO= Association for Research in Vision and Ophthalmology; SPIE = 

ineering; NR= not reported
Benefits and Harms of Femtosecond Laser Assisted Cataract Surgery Evidence-based Synthesis Program

9 29 CONTENTS 34

DISCUSSION

We conducted a systematic review of the current FLACS literature, comparing the benefits of 

FLACS to conventional cataract surgery, the adverse events associated with FLACS and the 

influence of increasing surgical experience on these adverse events. We found moderate evidence 

of comparable CDVA outcomes between FLACS and conventional cataract surgery groups. We 

noted limited evidence for a reduction of EPT in the FSL compared to the conventional cataract 

surgery group. Furthermore, meta-analyses found no statistically significant differences between 

FSL and conventional groups in either CDVA or EPT. No studies reported findings related to 

quality of life outcomes or cost effectiveness of FLACS relative to conventional cataract surgery.

Several studies reporting adverse effects unique to FLACS noted docking failures to be common. 

These failures were successfully managed by a subsequent docking attempt. Rarely did these 

failures require aborting the FSL procedure, with successful completion by converting to 

conventional cataract surgery, resulting in no adverse outcomes. There were moderate adverse 

findings of orbital or ocular anatomical laser interface difficulties, causing either aborted FSL

procedures or exclusion of these patients from the studies. The Catalys FSL platform, using the 

liquid-filled interface, was utilized in two studies of serial IOP measurements during and after the 

procedure. Transient elevation of IOP into the mid-20 to mid-30 mm Hg range during the FSL 

precedure was noted in these studies. No studies were found for IOP measurements using the 

Alcon LenSx FSL, which utilizes suction to effect docking. This interface mechanism has been 

noted to cause marked IOP elevations in other corneal refractive surgical applications.3

Most of the included studies reported on the comparative risks of adverse effects between FSL 

and conventional cataract surgery. Reports of adverse events were similar between FSL and 

conventional groups, including IOL positioning, corneal thickness, macular edema and residual 

refractive error. The rate of postoperative corneal endothelial cell was noted to be significantly 

decreased in the FSL group in only one included medium-sized study (N=201).16

The association between the experience of the surgeon and FLACS adverse effects was limited to 

three eligible studies, two of which were related. These studies reported mixed results of surgical 

experience reducing the incidence of FLACS adverse events, with very low strength of evidence.

We conducted an update search on September 18, 2013 and found two observational studies 

that reported decreased EPT with FSL,46,47 consistent with the trend seen among other studies 

included in our review. We also identified two recent studies that found decreased initial 

postoperative inflammation with FSL,47,48 although after three months no differences were 

observed between FSL and conventional cataract surgery.48

Although there were significant limitations with the body of literature, we found FLACS to 

be comparable to conventional cataract surgery. We found no evidence that FLACS differs 

from conventional cataract surgery on measures of safety and effectiveness. The unique risks 

associated with FLACS are primarily related to laser docking interface difficulties, which may be 

reduced with increasing surgical experience with the procedure. The comparative adverse event 

risks of FLACS and conventional surgery were similar. Complications rates in FLACS cohorts 

were found to be reduced or unchanged by surgical experience in the included studies of this 

review. 
Benefits and Harms of Femtosecond Laser Assisted Cataract Surgery Evidence-based Synthesis Program

9 30 CONTENTS 34

There were methodological concerns for the included studies that represent potential sources of 

bias that threaten the validity of study findings. Many studies had small sample sizes, with the 

potential for difficulty in analyzing data for low-risk events,49 and follow-up times and outcomes 

reported were often variable, making study comparisons problematic. In addition, study methods 

were often unclear, particularly with regard to the application of inclusion and exclusion criteria 

for FSL treatment groups and the enrollment of treatment and control cohorts. Often studies 

excluded patients with denser cataracts, comorbidities and those deemed uncooperative. In 

addition, many study protocols called for patients self-selecting into FSL or conventional surgery 

groups. Further, most studies evaluated similarities between treatment and control groups only 

for gender and age. 

All of the FSL platforms require the orbital anatomy to be accessible and the cornea to be 

suitable for successful laser docking. Two of the eligible studies in this review specifically 

excluded patients in the FSL group, who had “deep-set eyes”4 or “narrow palpebral fissures”.24

Similarly, an adequate laser/corneal interface requires a pristine corneal surface. Most of 

the studies excluded patients from the laser treatment groups with corneal pathology such 

as scarring, previous corneal surgery and high degrees of corneal astigmatism, limiting 

generalizability of findings to those patients for whom FLACS is appropriate.4,14,16,18,21-25

Similar exclusion criteria issues were noted in studies for dense cataracts18,22 as the FSL is 

unable to perform photo disruption in tissues that are not optically clear.4,50 The Schiempflug 

nuclear density grading (LOC III score of increasing density from 1-5) was reported at baseline 

in a minority of the comparative studies.4,16,18 Here, in the FSL groups, the LOCS III scores 

ranged from 2.13 to 2.59; only patients with mild to moderate density cataracts were enrolled, 

specifically excluding patients with dense cataracts. 

The FSL procedure is unsuitable for patients who are unable to cooperate, for any reason. Thus, 

some studies excluded patients from the FSL groups who were “uncooperative”,18 or with 

hemifacial spasm.24 Transient elevations of IOP limit FLACS suitability for patients with highrisk glaucoma, another exclusion criteria found in many studies. Patients with other medical 

co-morbidities, such as kyphosis and movement or behavioral disorders, were found to be 

unacceptable for FLACS procedures. The careful patient selection in studies of FLACS to date 

may significantly limit the generalizability of findings to VA cataract surgical populations. 

Operating room logistics and efficiencies are made more cumbersome by the need for a two-suite 

surgery staging for each patient.1

 Each patient undergoes the FLACS procedure beneath the FLS 

platform and is moved into a second, sterile location in the operating room for the completion of 

the surgery. In addition, multiple laser docking attempts can extend the operating room time for 

each patient. This added complexity and duration of the surgical procedure may adversely impact 

surgical backlogs. 

Device manufacturers are closely associated with most of the study authors and the majority 

of included studies (all but two) report financial conflicts of interest. Eligible studies were 

also clustered around a limited number of geographic sites and conducted by the same team of 

coauthors. All four of the included randomized trials were conducted by the same research group, 

and every surgery (FSL or conventional) was completed by the same surgeon study co-author. 

It is also unclear whether or not there was any overlap in the study patient populations of these 
Benefits and Harms of Femtosecond Laser Assisted Cataract Surgery Evidence-based Synthesis Program

9 31 CONTENTS 34

trials, given they were conducted at the same site and in what seems to be a similar timeframe.

Most of the studies in this review involved highly experienced, high-volume surgeons, supported 

by similarly experienced surgical teams. These findings may not apply to VA surgeons, especially 

with regard to ophthalmology residency training programs. The few studies which reported 

decreasing complication rates with increased surgical experience must be considered when 

evaluating the suitability of introducing FLACS into a training program environment. 

The eligible studies in this review did not include any cost-effectiveness or quality of life data. 

The non-laser portion of the disposable costs for FLACS and conventional phacoemulsification 

surgery are comparable, as both involve irrigation, aspiration and phacoemulsification. The 

additional, incremental cost of FLACS is the $150-300 per patient charge for the sterile, singleuse patient interface device.50 The approximate initial cost of the FSL equipment is $500,000. 

Future studies assessing the cost-effectiveness and incremental changes to quality of life 

associated with FLACS and conventional cataract surgery will be needed to provide additional 

information to guide procedure adoption decisions.

FUTURE STUDIES

Modern, conventional cataract surgery is associated with very low risks of sight-threatening 

complications.49 In this review, FLACS appears to be comparable to conventional cataract 

surgery, though the evidence base is limited. Greater numbers of randomized control trials 

(RCTs) with larger sample cohort sizes are desirable to allow detection of the relative risks 

of rare events. Assessment blinding is problematic, as FLACS patients are aware of their 

participation in the FSL treatment arm, as are the assessors due to the unique appearance of 

the laser versus the manual incisions. Studies that are sufficiently powered and well designed 

should be insulated from the device manufacturers to eliminate this potential bias. Head to head 

trials between FSL platforms should assist in informing potential users of their relative risks and 

benefits. Studies from groups other than those few included in this review should provide a more 

global perspective of FLACS. The applicability of the FSL technology to the overall cataract 

population has not been explored by the eligible studies in this review. Further studies regarding 

the suitability of FSL for patients with the co-morbidities found in the VA population (i.e. dense 

cataracts, glaucoma, corneal pathology) and studies assessing the costs relative to benefits 

expected from FLACS and conventional surgery will be key to determining the feasibility of 

widespread adoption of this procedure. 
Benefits and Harms of Femtosecond Laser Assisted Cataract Surgery Evidence-based Synthesis Program

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CONCLUSIONS

This systematic review found visual outcomes (CDVA) and EPT to be similar in FLACS and 

conventional surgery, while quality of life and cost-effectiveness outcomes were not reported. 

The evidence for the relative benefit of FLACS was limited by reliance on small to moderatelysized prospective cohort studies, nearly all of which had stated financial conflicts of interest. 

Adverse events unique to FLACS involved difficulties in laser docking or patient suitability 

for the procedure. Many patients were excluded from the FSL treatment groups for orbital, 

corneal, cataract density, or medical co-morbidities. Comparative adverse events in FLACS and 

conventional surgery were found to be similar for IOL positioning, corneal thickness, macular 

edema and residual refractive error. A few studies reported mixed results of the effect of surgical 

experience on the incidence of FLACS adverse events. 

Table 3: Summary of the evidence on the effects of femtosecond laser assisted cataract surgery

Outcome

For each study design:

Number of studies

(combined sample size)

Findings Strength of 

Evidence Comments

Visual acuity

2 RCTs (N=189)

4 NRCS (N=306)

No significant 

differences Low 

No differences in visual acuity outcomes found 

in either of the randomized trials. Unclear risk of 

bias for trials, low consistency, coherence and 

applicability of estimated effects across studies, 

small to medium sample sizes and conflicts of 

interest lower the strength of evidence.

Effective 

phacoemulsification time

1 RCT (N=76)

4 NRCS (N=615)

1 NCS (N=160)

Mixed findings Low

Trial found no significant reduction in EPT for FSL 

group. Two of the large nonrandomized studies 

(N=550) reported significant reductions in favor 

of FLACS. Remaining three studies found no 

significant differences. Unclear risk of bias for trial, 

low consistency, coherence and applicability of 

estimated effects across studies and conflicts of 

interest lower the strength of evidence.

Quality of life None None No evidence None of the included studies reported on quality 

of life outcomes. 

Intraoperative 

complications*

3 NRCS (N=1,900)

3 NCS (N=285)

Higher IOP 

for FLACS; 

Few additional 

complications 

for FLACS 

Moderate to 

Low

Low incidence of complications with FLACS, 

though increases in IOP reported across 

studies. Low applicability of estimated effects 

lowers the strength of evidence. 

Postoperative 

complications**

1 RCT (N=76)

1 NRCS (N=150)

1 NCS (N=160)

Mixed findings Low

Trial found no significant differences and mediumsized cohort study (N=150) found significantly 

reduced endothelial loss for the FLACS group. 

Unclear risk of bias for trial, low consistency and 

coherence of estimated effects across studies, 

small to medium sample sizes and conflicts of 

interest lower the strength of evidence.

Costs None None No evidence

None of the included studies reported on costs 

of FLACS compared to conventional cataract 

surgery.

Abbreviations: RCT = randomized controlled trial; NRCS = non-randomized comparative studies; NCS = non-comparative studies; 

FLACS = femtosecond laser assisted cataract surgery; EPT = effective phacoemulsification time; IOP = intraocular pressure.

*Intraoperative complications include: capsular blockage, capsular tear, dislocated nucleus, docking failure

**Postoperative complications include: infection, retinal swelling/cystoid macular edema, intraocular decentration, corneal edema
Benefits and Harms of Femtosecond Laser Assisted Cataract Surgery Evidence-based Synthesis Program

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48. Conrad-Hengerer I, Al Juburi M, Schultz T, Hengerer FH, Dick HB. Corneal endothelial

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1313.

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Benefits and Harms of Femtosecond Laser Assisted Cataract Surgery Evidence-based Synthesis Program

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APPENDIX A: SEARCH STRATEGY

MEDLINE (PubMed) searched 5/8/2013

Search Query

Search (#8) AND #7

Search ((((((femtosecond) OR alcon lensx) OR optimedica catalys) OR lensar) OR 

victus) OR intralase) OR ifs laser systems OR “all-laser Lasik”

Search (#6) OR #5

Search cataract

Search “Cataract”51 OR “Cataract Extraction”51

76 unique cites added to EndNote Library 

Cochrane Central Register of Controlled Trials and Database of Sytematic Reviews

(OVID), searched 5/8/2013

# Searches

1 exp Cataract Extraction/ or exp Cataract/ or cataract.mp.

2 femtosecond.mp.

3 alcon lensx.mp. [mp=title, original title, abstract, mesh headings, heading words, keyword]

4 optimedica catalys.mp. [mp=title, original title, abstract, mesh headings, heading words, 

keyword]

5 lensar.mp. [mp=title, original title, abstract, mesh headings, heading words, keyword]

6 victus.mp. [mp=title, original title, abstract, mesh headings, heading words, keyword]

7 intralase.mp. [mp=title, original title, abstract, mesh headings, heading words, keyword]

8 ifs laser systems.mp. [mp=title, original title, abstract, mesh headings, heading words, 

keyword]

9 All-laser lasik.mp. [mp=title, original title, abstract, mesh headings, heading words, 

keyword]

10 2 or 3 or 4 or 5 or 6 or 7 or 8 or 9

11 1 and 10

3 unique cites added to EndNote Library 

Additional databases, societies and journals, searched 4/17/2013 to 7/9/2013:

1. ASCRS: American Society of Cataract and Refractive Surgery http://www.ascrs.org/ [See

also abstracts that were locked out at end of document]

2. Journal of Cataract & Refractive Surgery http://www.jcrsjournal.org/

3. American Academy of Ophthalmology http://www.aao.org/

#9

#8

#7

#6

#5
Benefits and Harms of Femtosecond Laser Assisted Cataract Surgery Evidence-based Synthesis Program

9 38 CONTENTS 34

4. International Society of Refractive Surgery http://www.aao.org/isrs/

5. American Academy of Opthalmic Executives http://www.aao.org/aaoe/

6. The Foundation of the American Academy of Ophthalmology http://www.faao.org/

7. The Royal College of Ophthalmologists http://www.rcophth.ac.uk/

8. The Association for Research in Vision and Ophthalmology http://www.arvo.org/

9. The Journal of Cataract and Refractive Surgery http://www.jcrsjournal.org/

10. Ophthalmology, the official journal of the American Academy of Ophthalmology – http://

www.aaojournal.org/

11. COS Conference Papers Index

12. Proceedings First (OCLC)

13. http://clinicaltrials.gov/

14. http://www.fda.gov/
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9CONTENTS 34

LUSION/EXCLUSION CRITERIA 

Exclusion criteria/notes KQ1 – Benefits KQ2 –Adverse effects KQ3 – Learning curve

KQ1: What are the benefits of FLACS compared with conventional cataract surgery?

KQ2a: What are the unique risks associated with FLACS?KQ2b: What are the risks of FLACS compared to conventional cataract surgery?

KQ3: What are the intraoperative and post-operative risks of FLACS with regard to the experience f the surgeon?

y

Exclude studies of lasers used for procedures other than cataract surgery

Included interventions: femtosecond lasers used for cataract surgery applications 

Same interventions as KQ1 Same interventions as KQ1

 Note: FLACS is contraindicated in the following 

populations: advanced glaucoma; high anxiety; tremors; dementia; facial or ocular anatomy that precludes docking

Included population: adults undergoing cataract surgery 

Same population as KQ1. Same population as KQ1

Exclude non-systematic or narrative reviews, editorials and opinions. Add code B (e.g. X5-B) to consider using the article in Discussion, or possibly describe the study data as a lower level of evidence. 

Include controlled study designs:

• Randomized controlled

trials (RCTs)

• Non-randomized

controlled clinical trials

• Controlled before/after

studies

Included study designs for harms:

• Controlled studies• Quasi-experimental studies• Cohort studies• Case-control studies

Excluded study designs:

• Case reports• Case series

• Same study designs

listed for KQ2

• Cost-evaluation studies

Short-term patient outcomes:

• Visual acuity: postoperative day 1

Long-term patient outcomes:

• Visual acuity: after postoperative day 1 (typically

recorded after 1 week, 1month, or 90 days)

• Quality of life (QOL)

measures

Intra-operative complications:

• Capsular blockage syndrome• Dislocated nucleus• Capsular tear

Post-operative complications:

• Infection• Retinal swelling/cystoid edema

(CME)

• Intraocular (IOL) decentration• Corneal edema

Other reported harms

• Cost• All other specified

outcomes

Add comments or keywords as needed.Add to any of the above X codes (e.g., X5–B) 

if the article contains information that may be useful for the introduction, discussion, limitations, future research, or other contextual purposes. Add comments or keywords as needed.
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9CONTENTS 34

IBILITY CHARACTERISTICS OF STUDIES (PICOTS TABLE)

nce that FLACS is associated with 

han conventional cataract surgery?

KQ2: Adverse effectsKQ2a: What are the adverse effects that have been reported for FLACS? KQ2b: What is the evidence that FLACS is associated with a lower risk of adverse effects than conventional cataract surgery?

KQ3: Learning curveWhat is the evidence that the experience of the surgeon is associated with adverse effects of FLACS?

g cataract surgery. 

emtosecond laser surgery is relatively contraindicated in patients with: advanced glaucoma, high anxiety, tremors, dementia, facial or ocular anatomy that 

ate LASER docking (i.e. small palpebral fissures, prominent brows) and previous refractive surgery or corneal opacities.

er technology is used in cataract surgery to assist or replace aspects of conventional cataract surgery, including corneal incisions, capsulotomy and lens 

the point of commercial release include: Alcon LenSx (Alcon Laboratories, Fort Worth, TX, USA), OptiMedica Catalys (OptiMedica Corp, Santa Clara, CA, 

ensAR Inc, Winter Park, FL, USA), VICTUS (Bausch + Lomb, Aliso Viejo, CA, USA; and Technolas Perfect Vision GmbH, Munich, Germany), IntraLase FS 

stems (Abbott Medical Optics, Abbott Park, IL, USA). 

usive of studies of any femtosecond laser used for cataract surgery applications regardless of FDA status. 

aract surgery, defined as small-incision phacoemulsification with planned posterior-chamber intraocular lenses (IOL). 

including randomized controlled 

zed controlled clinical trials, controlled 

s and observational studies 

Controlled studies, observational studies, case-control studies, case reports, case series.

Controlled studies; observational study designs including economic evaluation studies).

e series and studies that do not 

ta such as editorials and non

ws.

Studies that do not report primary data such as editorials and non-systematic reviews.

Studies that do not report primary data such as editorials and non-systematic reviews.

t outcomes

y: post-operative day 1

 outcomes

y: after post-operative day 1

corded post-operative 1 week, 1

0 days)

fe (QOL) measures

Surgical Complications

• Intra-operative

• Capsular blockage syndrome• Dislocated nucleus• Capsular tear• Docking failure or loss of docking

• Post-operative

• Infection• Retinal swelling/Cystoid Macular Edema (CME)• Intraocular (IOL) decentration• Corneal edema

• Cost• All other surgical complications listed• Other adverse effects reported

efinition to be used for timing of patient outcomes is as follows: 

—patient outcomes on post-operative day 1

patient outcomes > after post-operative day 1 (no upper limit)

tandards for reporting timing of post-operative outcomes often have variable time-horizons. For example, potential harms such as CME or IOL decentration, 

from as early as post-operative day one or after months to years in some studies.
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9CONTENTS 34

ESSMENT OF METHODOLOGIC QUALITY IN STUDIES OF FEMTOSECOND 

CATARACT SURGERY

ol for observational studies

n-biased selection

High overall loss 

to follow-up or 

differential loss to 

follow-up

Adequate 

duration of 

follow-up

Outcomes prespecified and 

defined

Ascertainment 

techniques 

adequately 

described

Non-biased 

and adequate 

ascertainment 

methods

Statistical analysis of potential 

confounders

ized lens-softening

as

udy group and a 500 mm 

the other study group after 

on”

No NA Yes Yes Yes No 

“Descriptive statistical analysis was performed using SPSS. The ttest was used to compare the sample means. Boxplots were used for analysis.”

cheduled for elective 

d laser–assisted cataract 

NA. Primary outcome was intraoperative.

NA Yes Yes Yes Unclear

ond capsulotomies were 

n 48 eyes of 43 patients ...

 curvilinear capsulorrhexis 

was performed on 51 eyes 

ts, which served as a 

up”

No Yes Yes Yes Yes No

“Statistical analysis was performed by comparing two samples at a time using the Student t test for analysis of mean visual and refractive values and intraocular optical quality parameters in both study groups”

group comprised 12 eyes 

ts. The control group 

13 eyes of 13 patients.”

No Yes Yes Yes Yes Yes

puter randomization, 

d their right/left eyes were 

elected for femtosecond 

 surgery.”

No Yes Yes Yes Yes Unclear

ation was done using 

enerated tables”

No Yes Yes Yes Yes Unclear
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9CONTENTS 34

n-biased selection

High overall loss 

to follow-up or 

differential loss to 

follow-up

Adequate 

duration of 

follow-up

Outcomes prespecified and 

defined

Ascertainment 

techniques 

adequately 

described

Non-biased 

and adequate 

ascertainment 

methods

Statistical analysis of potential 

confounders

ere randomly assigned 

puter randomization) to 

p by the surgeon”

No Yes Yes Yes Yes Unclear

ere randomly assigned 

up using a computer 

on chart.”

No Yes Yes Yes Yes Unclear

ond capsulotomies were 

n 20 eyes of 20 patients 

 CCC was performed in 

20 patients undergoing 

gery with IOL implantation.”

No Yes Yes Yes Yes Unclear. GEE models used to 

correct for correlated measures for patients having both eyes operated.

cond laser-assisted 

sification with the LenSx 

m was carried out in 20 

0 patients with cataract. 

phacoemulsification 

med on 20 eyes from 20 

atients with cataract.”

No Yes Yes Yes Yes Unclear

ho underwent conventional 

rgery (i.e. did not have 

d laser) were classified as 

group”

No Yes Yes Yes Yes Unclear

150) included patients who 

ndergo femtosecond laser 

nt “

No Yes Yes Yes Yes Unclear

ve patients having 

d laser pretreatment to raction were recruited”

No Yes Yes Yes Yes Unclear
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9CONTENTS 34

n-biased selection

High overall loss 

to follow-up or 

differential loss to 

follow-up

Adequate 

duration of 

follow-up

Outcomes prespecified and 

defined

Ascertainment 

techniques 

adequately 

described

Non-biased 

and adequate 

ascertainment 

methods

Statistical analysis of potential 

confounders

cluded the initial 200 

e femtosecond laser 

rgeries, refractive 

nge surgeries, or both 

at the Vision Eye Institute “

No Yes Yes Yes Yes No

ive, multicenter, 

ized, postmarket 

undertaken after local 

approval was obtained for 

of the LenSx system”

NA. Primary outcome was intraoperative.

NA Yes Yes Yes Unclear
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9CONTENTS 34

ion’s tool for assessing risk of bias

uence generation Allocation concealment Blinding of participants, personnel and outcome assessors Incomplete outcome data Selective outcome reporting Risk of bias*

g computer 

on, patients and their 

es were randomly 

r femtosecond and 

gery.”

Unclear: No information provided

Unclear: No information provided, but one of the authors completed all surgeries, suggesting a lack of personnel blinding.

Low: Report no attrition and exclusions appear to all be pre-randomization.

Unclear: Reported on key outcomes but unclear if other outcomes were assessed but not reported.

Unclear

omization was done uter-generated tables”

Unclear: No information provided

Unclear: No information provided, but one of the authors completed all surgeries, suggesting a lack of personnel blinding.

Low: Report no attrition and exclusions appear to all be pre-randomization.

Unclear: Reported on key outcomes but unclear if other outcomes were assessed but not reported.

Unclear

nts were randomly 

sing computer 

on) to either group by 

n”

Unclear: No information provided

Unclear: No information provided, but one of the authors completed all surgeries, suggesting a lack of personnel blinding.

Low: Report no attrition and exclusions appear to all be pre-randomization.

Unclear: Reported on key outcomes but unclear if other outcomes were assessed but not reported.

Unclear

nts were randomly 

 each group using a 

andomization chart”

Unclear: No information provided

Unclear: No information provided, but one of the authors completed all surgeries, suggesting a lack of personnel blinding.

Low: Report no attrition and exclusions appear to all be pre-randomization.

Unclear: Reported on key outcomes but unclear if other outcomes were assessed but not reported.

Unclear

kely to seriously alter the results; 

hat raises some doubt about the results; 

 seriously weakens confidence in the results.
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R REVIEW COMMENTS AND RESPONSES

Comment Response

Question 1: Are the objectives, scope and methods for this review clearly described?

s. I think the objectives were well spelled out. We did not ask specifically for any cost/benefit analysis so 

s done nicely.

Noted, thank you.

s. (No comment) Noted.s. (No comment) Noted.s. The objectives could be more clearly stated as the purpose of this work is to systematically review and 

ically appraise the available evidence of FSL assisted cataract surgery vs conventional surgery.

We thank the reviewer for the comment. The reviewer is correct that one aspect of the review is to appraise available evidence of FSL compared to conventional cataract surgery. However, the harms and learning curve assessment questions were not limited to comparative studies. We have clarified the objectives of the report in the background and methods sections.

n of bias in our synthesis of the evidence?

. I did not see any, but the papers reviewed certainly had bias as you pointed out. Noted, thank you.. (No comment) Noted.. (No comment) Noted.. (No comment) Noted.

hed or unpublished studies that we may have overlooked?

. None that I am aware of. Noted.

. (No comment) Noted.. Given the technology is fairly new as far as FDA approval, high level evidence literature is limited. Noted.

s. Methods: The recommended databases to search (as a minimum) by the Cochrane Collaboration is 

MBASE, MEDLINE, and CENTRAL. I suggest reviewing EMBASE and CENTRAL in addition to all the 

er sources searched.

We have clarified the databases searched in Figure 2 (literature flow) of the report. Our search of the Cochrane library included the CENTRAL register of controlled trials. Unfortunately, our library does not subscribe to EMBASE so we do not have access to that database. However, we are reasonably confident that we have captured the relevant literature for the topic, given that we have searched the grey literature and recent conference proceedings in this quickly evolving field.
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Comment Response

al suggestions or comments below. If applicable, please indicate the page and line numbers from the draft report.

ere any of the papers quoted funded directly by manufacturers? It seems like even in the papers quoted 

u had methodological questions, for instance were patients used in multiple reports and that most of the 

tter” papers were all done by one surgeon, so the question of learning curve remains?

We examined the acknowledgements listed for each of the papers and could only report on the consulting fees and honoraria received by study authors. In addition, there were very few papers examining the issue of learning curve. As a result, the evidence available to answer key question 3 is very sparse. 

ppreciate the amount of effort the coordinators have made for this systematic review. I have the following

mments. A limitation of meta-analysis restricted to methodologically sound comparison studies is failure to

pture relatively infrequent but important adverse outcomes that begin to be reported as individual or small

ies reports several years after institution of a new technology. This pattern was seen in corneal refractivegery after institution of LASIK (laser in situ keratomileusis). Case reports of ischemic optic neuropathy

terior or posterior) with partial loss of vision were linked to the high intraocular pressures from the

tal suction rings used for the standard microkeratome procedure (references 1-3). A similar case of

ic neuropathy has been reported with a femtosecond laser using a low-pressure suction ring (reference

 As a LASIK surgeon, I am aware of other unreported cases. As you note in your review, all docking

vices currently used in femtosecond platforms lead to an increase in intraocular pressure, which puts the

crocirculation of the optic nerve at risk, especially in patients with microvascular disease from diabetes or

pertension. This effect may be especially important in the VHA population. Ischemic optic neuropathy has

o been reported after uncomplicated conventional phacoemulsification (References 5-7).

ferences.

1. Lee AG, et al. Optic neuropathy associated with laser in situ keratomileusis. J Cataract Refract Surg

2000;11:1581-4.

2. Bushley DM, et al. Visual field defect associated with laser in situ keratomileusis. Am J Ophthalmol

2000;129:668-71.

3. Cameron BD, et al. Laser in situ keratomileusis-induced optic neuropathy. Ophthalmology

2001;108:660-5.

4. Maden A, et al. Nonarteritic ischemic optic neuropathy after LASIK with femtosecond laser flap

creation. J Neuro-Ophthalmol 2008;28:242-3.

5. Lee H, et al. A case of decreased visual field after uneventful cataract surgery; nonarteritic anterior

ischemic optic neuropathy. Korean J Ophthalmol 2010;24:57-61.

6. Luscavage LE, et al. Posterior ischemic optic neuropathy after uncomplicated cataract extraction. Am

J Ophthalmol 2001;132:408-9.

7. McCulley TJ, et al. Incidence of nonarteritic anterior ischemic optic neuropathy associated with

cataract extraction. Ophthalmology 2001;108:1275-8.

We thank the reviewer for the insightful comments. In an attempt to identify all of the adverse events associated with FLACS, we included various study designs, even those of case reports. As the reviewer points out, these low prevalence events are not appropriate for meta-analysis. As noted in our review, all of the FSL platforms have been associated with some elevation of IOP during the procedure. This has not been noted to be as severe as the amaurosis-inducing levels common with LASIK procedures, which generate high IOPs with the use of microkeratomes. Our report does reflect the concern with even mild elevations of IOP being potentially harmful to glaucoma patients and may therefore exclude Veterans with this common comorbidity from being candidates for FLACS.
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Comment Response

u mention disposable costs for FLACS of $150-300. What are the disposable costs for conventional

aco?

Our review has been amended to reflect this cost issue. The disposable costs of FLACS and conventional phacoemulsification surgery are comparable (both involve irrigation/ aspiration and phacoemulsification procedures). The additional incremental cost of FLACS is the $150-300 per patient charge for the sterile, single-use patient interface device.

e draft report addresses on point the request for information. Noted.e review covers as one of its key questions “What is the evidence that the experience of the surgeon 

associated with adverse effects of FLACS?” a couple studies showed less adverse events with more 

perience with FLACS. It would be nice to compare the surgical learning curve of FLACS vs Conventional 

aract. There is some early literature in presentation and poster on this...not sure publications exists. This 

 be key for the VA given it is very involved in resident cataract surgery teaching.

ckett, 201340

ial Resident Experience Performing Cataract Surgery with and without Femtosecond Laser

onference proceeding)

VO Poster Session, 2013

Thank you for the comment. However, the comparative learning curve of FLACS versus conventional surgery is outside of the scope of the review. This will be important in future questions of learning curve comparing surgical procedures (conventional compared to FLACS)

hough meta-analyses of observational studies are not as frequent as for RCTs, there are guidelines 

OOSE) that are accepted to estimate summary effects based on observational studies. Nonetheless, if 

 authors consider that the quality of the observational studies (e.g., bias) preclude a meta-analysis, then 

ok not to do it.

We thank the reviewer for the comment, and agree that the concerns with the included observational studies preclude meta-analyses of additional outcomes. 

 and Implementation Questions

ical performance measures, programs, quality improvement measures, patient care services, or conferences that will be directly affected by this report? If so,

ne that I am aware of. I have heard of several more machines being requested and some purchased 

oss the VA system. 

Noted.

e report supports the FDA approval of this technology Noted.

. (No comment) Noted.

ecommendations on how this report can be revised to more directly address or assist implementation needs.

ne. The way I interpreted your results was that there was weak to moderate support of some advantages 

his technology but the same for the adverse effects. Even this information is generated from reports that 

ve either stated or possible conflict of interest. While not in your prevue, I am hoping this report can be 

bmitted with any application for technology across the VISN.

Noted, thank you for your comment.

 recommendation Noted.. (No comment)
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Comment Response

methodology there are some issues that should be addresed: 

TA ANALYSIS:

w heterogeneity was assessed and examined (stratification, regression)?, how bias was evaluated ? , ich effect measure was used for meta-analysis and which weighting method (random, fixed models)?

o, it should be stated that STATA was used for statistical analysis. 

We have provided more information in the methodological details of the meta-analyses. All analyses were conducted in StataIC 11, and we assessed the presence of statistical heterogeneity among the studies by using standard chi-square tests, and the magnitude of heterogeneity by using the I2 statistic. We explored models using 

both mean and ratio of means (SoM) based on a random effects model (combining means used the DL method and combining SoM used the PL method) – however, we do not report the combined estimates due to too much heterogeneity and rely on the forest plots as a visual aid for readers.