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

9 37 CONTENTS 34

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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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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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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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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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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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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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.