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.

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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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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