**Transcript of Cyberseminar**

**Evidence-based Synthesis Series**

**Benefits and Harms of Femtosecond Laser Assisted Cataract Surgery - A Systematic Review of the Evidence**

**Presenters: Dr. Ken Gleitsmmann, Dr. James Orcutt, Dr. Elizabeth Baze**

**April 29, 2014**

*This is an unedited transcript of this session. As such, it may contain omissions or errors due to sound quality or misinterpretation. For clarification or verification of any points in the transcript, please refer to the audio version posted at www.hsrd.research.va.gov/cyberseminars/catalog-archive.cfm or contact**ken.gleitsmann@gmail.com*

Moderator:Thank you everyone for joining us for today’s spotlight on “Evidence-Based Synthesis Program” cyberseminar session. Today’s session is “Benefits and Harms of Femtosecond Laser Assisted Cataract Surgery, A Systematic Review”. Our presenter today is Dr. Ken Gleitsmmann, he is an ophthalmologist in Hilton Head, South Carolina and Clinical Evidence Specialist with the Center for Evidence Based Policy with Oregon Health and Science University. He will be joined today by two discussants, Dr. James Orcutt, Chief of Ophthalmology with the Office of Patient Care Services with the Veterans Health Administration and also Adjunct Professor, Department of Otolaryngology with the University of Washington. Our second discussant today will be Dr. Elizabeth Baze, Staff Ophthalmologist with the Michael E. DeBakey VA Medical Center and Assistant Professor of Ophthalmology with the Baylor College of Medicine. And Dr. Gleitsmann can I turn things over to you?

Dr. Ken Gleitsmann:Yes thank you Heidi. Good afternoon everyone, thank you for logging in to today’s cyberseminar on the “Benefits and Harms of Femtosecond Laser Assisted Cataract Surgery”. This presentation is based on systematic evidence review conducted by the VA Evidence Synthesis Program in Portland, Oregon. I would like to acknowledge the report authors: Ana Quinones, myself along with Michele Freeman, Rochelle Fu, Maya O’Neil, Makalapua Motu’apuaka and Devan Kansagara. I would also like to acknowledge our report nominators and reviewers for the topic. The topic nominators were:  Drs. William Gunnar and James Orcutt. We received reviewer comments on the report from Dr. Orcutt as well as Amy Chomsky, Glen Cockerham, Mary Daly and Mary Lawrence. Drs. Orcutt and Baze will be joining the Q&A discussion as Heidi just mentioned following the slide presentation. 

Disclosures, briefly this report is based on research that we conducted by the VA Evidence Synthesis Program funded by the Department of Veterans Affairs. However the findings and conclusions of this document are solely the responsibility of the authors. 

The VA ESP Program overview is an evidence based synthesis program ESP sponsored by VA QUERI, the Quality Enhanced Research Initiative. This program was established to review evidence on healthcare topics that are identified by the VA leadership for improving the health and healthcare of veterans. There are four VA ESP Centers located at the Durham, the Greater Los Angeles and the Portland VA Medical Centers, and Minneapolis VA Medical Center. 

Evidence reports are used to develop clinical policies to support VA Clinical Practice Guidelines and performance measures and to inform the implementation of services to improve patient outcomes. It also identify gaps in evidence and guide future research directions. Topics of the evidence reviews may be nominated by any one. The process nominated topic is available to the general public on the ESP website. A coordinating Center for the ESP Program Reviews, the nominated topics for further consideration. 

A Steering Committee representing research and operations provides oversight and helps guide the program direction. We also received guidance from our Technical Advisory Panel with expertise on each particular topic. The Technical Advisory Panel provides the inputs on our research questions and topic developments, reviews our findings and provides feedback on our draft report.  We also invite External Peer Reviewers and Policy Partners to review and provide comments on draft reports. The final reports are posted on the VA HSR&D website and they are disseminated widely through the VA. 

The current report its benefits and harms of Femtosecond Laser Assisted Cataract surgery which returns FLACS and this is a systemic review that was dated December, 2013. 

The overview of today’s presentation will be a background for the review; the scope of the review; its results, limitations and comments on future research directions and the implications will be a part of the panel discussion that Heidi mentioned. 

In terms of background for the subject, current preferred methods for removing cataracts includes creating corneal incisions manually along with anterior capsulomoties followed by phacoemulsification. Recently these three manual procedures have each been perfumed in an automated fashion with the use of the femtosecond laser.  Studies have suggested that decreased phacoemulsification energy use with FSL cataract surgery and also have examined the potential advantages of a more precise corneal incision and capsulotomy formation. 

Cataract surgery is frequently performed in the Veterans Hospital Administration more than forty-nine thousand were performed in the year 2012. The VA National Surgery Office has been tasked with making a recommendation on whether this technology will provide appropriate cost-benefit and risk-benefit ratios to support implementation for cataract surgery within the VA. The purpose of this systematic review is to examine the effectiveness and the safety of the femtosecond laser assisted cataract surgery relative to its conventional counterparts in cataract surgery.

The scope of the review key questions which were developed by our stakeholders include Key question number 1 which is – what is the evidence that FLACS is associated with better outcomes than conventional cataract surgery? Key question number two was broken down into two parts: a)  what are the adverse effects that have been reported for FLACS that would be unique to FLACS; b) what is the risk of adverse effects from FLACS compared to the risk of associated risks in conventional cataract surgery? Then key question number three – what is the evidence that the experience the surgeon is associated with adverse effects of FLACS? 

Inclusion criteria for the review or patients who are undergoing cataract surgery, the intervention was femtosecond laser technology in all three of the steps in cataract surgery. The comparator was conventional cataract surgery. This was defined as small-incision surgery with phacoemulsification and posterior-chamber lens intraocular lens (IOL) implantation. The outcomes of interest were visual acuity in the short term, post-operative day one and also long term outcomes anything after post-operative day one with no upper limit. Also the outcomes for quality of life and the outcomes for harms. Study designs were open to controlled trials either randomized or non-randomized and observational studies comparing FLACS to conventional cataract surgery.

The analytic framework diagram seen here shows the relationship between the key questions and the study parameters. Again key question number one asks how effective FLACS is compared to conventional cataract surgery on short and long term outcomes and quality of life. Key question number two asks about adverse events again broken down into those unique adverse events to FLACS and those comparative to standard cataract surgery. Question number three asks whether there is any evidence on the learning curve affecting the benefits and harms for FLACS. 

The exclusions of the review were those articles that appeared in non-English language; non-adult study populations. Those articles or studies with no primary data such as editorials or non-systematic review articles. Also outcomes that were not in scope for instance ex-vivo studies. 

We then developed a search strategy of terms and subject headings, applied the search strategy to the MEDLINE database and the Cochrane Library of Control Trials and Systematic Reviews. We also search for in progress studies via clinicaltrials.gov and conference proceedings. The societies we search for conference proceedings included the American Society of Cataract and Refractive surgery; the *Journal of Cataract and Refractive Surgery*, the American Academy of Ophthalmology, *Ophthalmology Journal*, International Society of Refractive Surgery, the American Academy of Ophthalmic Executives, the Foundation of the American Academy of Ophthalmology and the Royal College of Ophthalmologists. 

After running the search and assembling our library, we applied the inclusion/exclusion criteria to select relevant studies. and based on the scope parameters I mentioned earlier, that is population, intervention, comparators, outcomes and study designs. We have abstracted the uniform data elements from each study including the study design, the objectives. The setting was important in terms of country and institution information, population characteristics including demographic information, medical comorbidities, subject eligibility and exclusion of criteria. The number of subjects, duration of follow up and the study and comparator interventions, the health outcomes, adverse events and number and experience surgeon. We also rated the quality of studies which was done by two investigators independently. For the observational study qualities we used criteria based on the New Castle Auto-Scale. For the randomized trials we used the Cochrane Collaboration Tool for assessing risk of bias. In addition, quality criteria such as financial and conflicts of interest were investigated. We did notice that a number of studies were being produced by the same authors or groups of authors which we called Same Team Replication. We took these factors into account when determining the quality and limitations of the evidence. 

Our Search Yield, the combined Search Yield at nine hundred and four titles and abstracts. After reviewing each one we selected seventy articles and conference abstracts for further review at the full text level. 

We selected fifteen studies for inclusion in the review based on the parameters I mentioned in the earlier slide. 

I will interject a poll question here and ask that the audience pick one answer that is – what best describes your professional training. Number one – ophthalmologist; number two – optometrist; number three – researcher; number four – other and lastly no vote. So it looks like we have a mix of ophthalmologists, researchers and other. 

One further poll question. For the practicing ophthalmologists if you would pick on answer. What best describes your experience with FLACS. One – a practicing ophthalmologist with FLACS experience; two – practicing ophthalmologist planning to perform FLACS in the future; three – practicing ophthalmologist not planning to perform FLACS n the future. It looks like we will wait just a minute. So we do have a fair number of participants who have been using the laser thirty-three percent and those not planning on using FLACS technology are sixty-six percent of the audience. 

We will turn to the results of the review and we will take these by key question. The first of which is – what is the evidence that FLACS is associated with better outcomes than conventional cataract surgery. Visual outcomes that is corrected distance visual acuity were similar between these two comparative groups. The effective phacoemulsification time which is a derived figure based on the phacoemulsification time and the phacoemulsification power, these outcomes were mixed and the results were either comparable between groups or the favored the Femtosecond Laser groups. These were the two most common outcomes reported and therefore meta-analysis of these outcomes was performed however, there was heterogeneity that precluded calculation of a reliable summary effect estimate. We will have more to say about this in a moment. No studies addressed quality of life issues or measures. 

This is a Forest Plot which shows the outcome of corrected distance visual acuity post-operatively. And this is just shown to illustrate the point just made that the findings of studies were essentially similar between the conventional and the FLACS groups. 

Another Forest Plot represented here for effective phacoemulsification time shows that the findings were either similar or favoring FLACS. That is to say that the effect of phacoemulsification time is decreased with FLACS over the conventional surgery. 

Continuing results of key question 2A now, one of the adverse effects that have been reported for FLACS these are specific or unique to FLACS. These we found fell along two lines – laser interface events and also intraocular pressure events. Laser interface events and there were several studies which showed significant numbers of patients which required a second docking attempt but these proceeded without adverse effects. There were also patients with corneal scar and distortion or  kyphosis or claustrophobia or excessive movements which were excluded from Laser treatment groups. In the instance of intraocular pressure events, all of the Femtosecond Laser document platforms have been shown to cause increases in intraocular pressure which is a theoretical concern for patents with coexistent glaucoma. However the two studies that were included in this review were noted IOP effects and they were using only the Catalys Femtosecond Laser on platform. One of these case series with a hundred patients noted a mean IOP which increased to the level of 27.6 plus or minus 5.5 millimeters of mercury. In another smaller case series, the mean IOP increased to a level of 36.0 plus or minus 4.4 millimeters of mercury. 

The key question 2B which was the comparative risks of FLACS versus conventional cataract surgery, comparative risks of adverse events they were need to have similar findings for post-operative corneal edema, macular thickness and macular morphology. There were methodological concerns noted for these comparative results as the enrollment criteria vary between the conventional and the laser surgery groups. 

Key question number 3 which was regarding evidence of the experience of the surgeon being associated with the adverse effects of FLACS. The overall findings were again mixed an studies comparing initial to subsequent groups of patients who are undergoing FLACS. In one study it was noted that surgeons who had extensive refractive surgery experience had fewer complications in their earlier FLACS patient groups then did surgeons without previous refractive surgery experience. Again, methodological concerns were noted in the enrollment criteria between the two groups. 

Limitations of the evidence. The mythological concerns were those of small sample sizes and also selected samples which excluded patients that were unsuitable for FLACS. That is to say patients would have been included in the conventional cataract surgery that would not have been FLACS candidates thereby making these two groups unequal. So the selected samples that were unsuitable for FLACS were such as patients with dense cataracts or orbital anatomy which was incompatible with successful Laser docking. Also concerns of conflicts of interest the same team replication which was mentioned previously and also many or most studies were funded by the industry. 

This is a table which summarizes the evidence for benefits for FLACS and again illustrating on the left side of the slide the outcomes of visual acuity, effective phacoemulsification time and then quality of life outcomes. The number of studies are reported here, these are randomized control trials and non-randomized control trials. The findings for visual acuity again, no significant differences between the comparative groups, the effective phacoemulsification time had mixed findings and there were no findings for quality of life outcomes. The strength of the evidence because of the study designs the sample size and the previously mentioned limitations of the evidence found low strength of evidence for visual acuity outcomes and EPT and no evidence for quality of life outcomes. The comments have been mentioned previously. 

A similar table is shown here summarizing the evidence for harms and the number of studies and the outcomes. The intraoperative outcomes were those of higher intraocular pressure and essentially few additional complications for FLACS. Those would have been capsular tears, capsular blockage, dislocated nucleus and docking failures. For post-operative complications findings again the rate of post-operative complications comparing the two groups noted mixed findings and post-operative complications with those of infection, retinal swelling, cystoid macular edema, intraocular lens decentration and corneal edema. Again, findings of a low strength of evidence for these outcomes with the comments previously noted. There were no cost studies and therefore no evidence for cost comparisons between FLACS and conventional cataract surgery in the eligible included studies. 

A comment about a future research suggestions it would be important for randomized control trials to be conducted with larger sample sizes especially to detect rare events of the rates in conventional surgery being so low in a comparable technology would have to have large sample sizes to detect these rare events. The application of the Laser technology to patients with dense cataracts, glaucoma and corneal pathology should be addressed. Head to head trials between the various Femtosecond Laser platforms that would be important and of course studies which would illustrate cost benefit ratios would also be of importance. 

I will be happy to entertain questions about the evidence report and look forward to the discussion by our discussants. 

Moderator:wonderful thank you so much Dr. Gleitsmann. Why don’t we take a few moments and listen to our discussants and see what they would like to talk about. While we are doing that, to our audience please feel free to submit your questions using the Q&A screen. We would love to have a few moments to prepare answers for that. Do not hesitate to send any questions in. Dr. Orcutt would you like to take a few moments here?

Dr. James Orcutt:Thank you I guess you can hear me okay. 

Moderator:We can hear you  yes. 

Dr. James Orcutt:Okay, great. Well just a few things. One is that I would like to correct your titles. I think when this all started I was the  Program Director for Ophthalmology at Patient Care Services. That subsequently now Dr. Cochrane fills that position, I have stepped down from that so I am still Professor of Ophthalmology at the University of Washington and Chief Surgical Consultant. I take it the time it started as I said and I may have been the Program Director when we first started talking about submitting this. 

The reason this all came to pass was that there are sites within the VA which have now purchase Femtosecond Lasers and the question arose how these lasers would be  ideally incorporated into current practice within the VA. That arose a question about what really is the benefit from a clinical point of view other than the fact that it is new technology and quite amazing technology. Is it really cost advantageous for the VA to be purchasing these lasers if we are not really getting a secondary positive benefit for the patients. I guess I look at this from a point of view that is a cup half empty and a cup half full. Apparently I think that the way I interpret the data from the ESP group was that there is no strong data supporting the use of a Femtosecond Laser over conventional cataract surgery at least for the parameters we looked at. There is no doubt that the technology itself is fairly expensive but being incorporated a lot more commonly in the private community. 

That was basically what was in my mind to bring to this to the forefront for the ESP group is that is there advise that we should be providing about the facilities and VISNs considering buying such equipment in terms of how it is really going to benefit veterans. From what I can glean from what we have in the reports so far is that there really no strong evidence that we would do any better with this equipment then we do with conventional cataract surgery. 

Unfortunately just after this study was closed and the literature support there are at least two and maybe more that I am not aware of. But at least two additional reasonably well controlled trials published looking at cost benefit for Femtosecond Laser and also looking at the risks associated with capsular rexus with cataract surgery. Both of those not again showing a strong support for cost benefit nor for an increased outcomes with cataract surgery. Now others and Dr. Baze certainly may have more literature because that is just a sampling of the literature. I still feel that along the discussion should take place in terms of incorporating this technology into the VA. 

That was my reason for bringing it to pass. I do not know, I think the study has not convinced me to change my opinion about the lack of cost benefit or risk benefit to the VA system. As I said that is a cup half full a cup half empty type of approach. I do think that the one thing that the VA is ideally suited for at this point of time with the number of lasers that are purchased and are being purchased within the VA system is that we are ideally set up to do some of these research trials looking at a controlled comparison of Femtosecond Laser versus conventional cataract surgery. I would strongly encourage those sites with the laser to consider the possibility of a multi-centered clinical trial looking at some of the research opportunities so we can really answer this question. 

That is all I have to say at this point. 

Moderator:Wonderful, thank you so much Dr. Orcutt. Dr. Baze?

Dr. Elizabeth Baze:I think I agree with Jim in terms of how to look at this report and the data that is out there thus far. I would say that I wonder how much we will see that change given software updates and improvement to the current platforms that are available. I think that it would actually be very interesting to see a head to head comparison of the available platforms here in the U.S. because to sort of anecdotally it does seem there may be a difference in terms of particularly  the nuclear fragmentation. We do have a Femtosecond Laser and we started using it, started getting our staff physicians certified on it and then subsequently residents and fellows. At the end of 2013 and kind of ongoing now, I would say that things to consider are that it is certainly not for everyone, and I think that that is fairly well known. I think patients do like the idea of having it available to them because I feel like it gives them a sense of I get the same thing here at the VA that I would outside which is I think nice to have. I am not sure that you could really put a price tag on that or really justify the purchase based on hat perception alone. 

The other thing that I would say is that the operative times are definitely longer because it is one more thing to add into your OR sequence. Most places we place the laser outside the actual operating room, but somewhere close to the operating room. We have ours outside our operating rooms in a separate area n between the ORs that we use. But it does tack on at least another ten to fifteen minutes to the case logistically. Some of what we are seeing now may still be residual effects of a learning curve in terms of how to manage, not only the laser itself and doing the laser procedure which is fairly simple once you have been trained but also then removing the cataracts. The technique is slightly different and there is a learning curve obviously to that. 

I think the third thing I would say is that we are probably seeing in our initial cases when we were doing our certification we did see probably more of the complications that you see specific to Femtosecond Laser assisted cataract surgery which would have been a capsulotomy adhesions, micro-adhesions and anterior capsular tears. We really do not see much of that anymore and that may be related more to the surgeon awareness of that as a potential complication just being able to handle it a little bit better. 

The one thing I will say about the Laser is that I have not been if you talk to most surgeons who are using Femtosecond Laser that the creation of corneal wounds, both the phaco-wound and the parenthesis wounds are not as predictable and reliable as we would probably like. That is something to consider. I think most people do not really look at that as a huge advantage of using the laser obviously. The LRIs that the lasers can provide are very nice and I think that is certainly a big plus to them. 

I see that there is a question about introducing residents to cataract surgery and how to incorporate Femtosecond Laser into teaching resident surgery within the VA. We are certifying only our third year residents and only towards the end of the academic year when we feel that they are very competent manual phaco-surgeons. We do have a high volume program and most of our residents will do two hundred cases or upwards of two hundred phaco-cases. We do have a high volume program and most of our residents will do two hundred cases or upwards of two hundred phaco-cases as primary surgeon throughout their training and about two-thirds of that would be here at the VA. 

I think that it is technically different enough where I think it is really important that residents have a good bases and really know how to operate before they started getting into Femtosecond technology. I do not think that it is necessarily appropriate to use it as a stepwise introduction to phaco. Meaning okay you have your capsulotomy formed so that is one step you do not mind how to do. I think from a training perspective it should more of a higher level technique rather than introducing it in the early stages when they are more novice surgeons. 

I guess I will stop there, I do not know if anybody has any questions about actual implementation of using this technology. But I do agree I think it is a nice thing to offer the veterans. I cannot tell that our outcomes are any different from manual phaco and oftentimes the patients ask me should I have the laser should I not, I tell them I am faster without it and I think the results are just as good. But some patients really like the idea of the laser and we have it and we use it in certain selected cases. 

Moderator:Great thank you. Dr. Baze did cover the one question we receive in so far. If anyone in the audience if you have any questions you would like to send in. Fantastic we are getting some more in. Please take this opportunity we do have some time for questions here. The next question that we have – what is the overall added cost to introduce FLS?

Dr. Ken Gleitsmann:I am going to have to defer to Dr. Baze since she actually has the laser. I know in the non-VA world there is a cost for the laser and then there is a per-treatment fee that is also generated every time the laser is used. I defer to her on how that has been managed in the VA system. 

Dr. Elizabeth Baze:The patient interfaces for the unit that we have and I would have to get back to you on that exactly what we paid for the laser, it was approved about a year and a half ago. The patient interface, so per case cost is about four hundred dollars. It is not insignificant and that is definitely added on. Plus you have to think about you have a technician that you have to train to operate the laser. For us that is somebody that is not stationed in the operating room, that is actually one of the ulsonic technicians and our clinic will go up so you are taking them away from other duties downstairs. It is not only a little bit of a manpower issue, but obviously the per case cost necessarily goes up. So it is not something that you would want to do all of your cases with. I think it may have some advantages if you think about patients who have loose zonules and you want a good capsular excess and maybe a head start and finding the nucleus so they might reduce the amount of stress on the bag that is a  potential advantage. After you start doing multi-focal lens and I do not know if any of the VA’s actually have a consignment on multi-focal lenses rhetoric lenses it is nice for premium lens patients. That is I would assume a relatively small percentage of patients going into cataract surgery. 

Moderator:Great thank you. We do not have any other pending questions at the this point. If anyone else would like to send in a question please do that. I just want....

Dr. James Orcutt:This is Jim I am going a question which I have not actually dealt with. Does the VA pay that four hundred dollars per patient treatment to the company? Is that the way it is set up with the company?

Dr. Elizabeth Baze:I believe that is the case. We order the patient interfaces it is a supply that we order just like we order phaco-packs. 

Moderator:That is totally fine. I was actually just going to ask if any of our presenter or discussants have any other or final remarks you would like to make before we wrap things up today. 

Dr. Ken Gleitsmann:This is Dr. Gleitsmann. I just had two comments. One in the private world, the laser and I can only speak for a LenSx Laser which has the market share of the U.S. that is the Alcon product. That is roughly five hundred thousand dollars and a hundred thousand dollars per year in a maintenance contract. The patient interface which is basically disposable their latest interface is roughly two to two hundred and fifty dollars per patient. Those are the costs. 

Another comment I had that sort of occurred to me with the question about resident surgery. It was obvious to the evidence team that every single one of these studies was produced in an area where very, very most experienced surgeon. And one institution only a single surgeon was doing all of these cases which certainly is not the experience for our residents comparing their early experience with someone who has been doing it for a long period of time. Just an interesting comment. 

Moderator:Great, thank you. Dr. Orcutt, Dr. Baze do either of you have anything final you would like to remark before we close things out today?

Dr. Jim Orcutt:Just to say thanks we have been working with you for a little while on this and thank the ESP folks for such an in-depth quality review. I think the way you attack the data and present it and evaluate it is excellent and I really appreciate all your help. 

Moderator:Great thank you. For our audience I want to thank everyone for joining us today. If you could stay for just a moment we have just put up a feedback form if you could take a few moments to fill that out we would very much appreciate it. While you are doing that I really want to thank Dr. Gleitsmann, Dr. Orcutt and Dr. Baze for taking the time to prepare and present at today’s session. We very much appreciate the time that all three of you were able to put into today’s session. For our audience thank you for joining us today and we do hope to see you at a future HSR&D Cyberseminar. Thank you everyone for joining us. 

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