UNITED STATES OF AMERICA

 

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           FOOD AND DRUG ADMINISTRATION

        MEDICAL DEVICES ADVISORY COMMITTEE

 

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         OPHTHALMIC DEVICES ADVISORY PANEL

                   106^TH MEETING

 

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                      FRIDAY,

                  OCTOBER 3, 2003

 

      The panel met at 8:30 a.m. in the Gaithersburg Marriott Washingtonian Center, 9751 Washingtonian Boulevard, Gaithersburg, Maryland, Dr. Jayne S. Weiss, Chair, presiding.

 

PRESENT:

 

JAYNE S. WEISS, MD., Chair

ARTHUR BRADLEY, Ph.D., Member

MICHAEL R. GRIMMETT, M.D., Member

ALICE Y. MATOBA, M.D., Member

TIMOTHY T. McMAHON, O.D., Member

ALLEN C. HO, M.D., Member

ANNE L. COLEMAN, M.D., Ph.D, Member

KAREN BANDEEN-ROCHE, Ph.D, Consultant,

                     deputized to vote

WILLIAM D. MATHERS, M.D., Consultant,

                     deputized to vote

JOEL SUGAR, M.D., Consultant, deputized to vote

MARIAN S. MACSAI-KAPLAN, M.D., Consultant,

                     deputized to vote

JAMES P. McCULLEY, M.D., Consultant

OLIVER D. SCHEIN, M.D., Consultant,

                     deputized to vote

GLENDA V. SUCH, M.Ed., Consumer Representative

R. MICHAEL CROMPTON, J.D., M.P.H., R.A.C.

                     Acting Industry Representative

SPONSOR'S PRESENTERS:

 

HENRY F. EDELHAUSER, Ph.D

HELENE LAMIELLE, M.D.

DONALD R. SANDERS, M.D., Ph.D.

STEVEN G. SLADE, M.D.

JOHN A. VUKICH, M.D.

 

FDA PARTICIPANTS:

 

A. RALPH ROSENTHAL, M..D.

GERRY W. GRAY, Ph.D.

DONNA R. LOCHNER

MALVINA B. EYDELMAN, M.D.

SARA THORNTON

 

OPEN PUBLIC HEARING SPEAKER:

 

CAPT. STEVEN C. SCHALLHORN, M.D.

 

                  C-O-N-T-E-N-T-S

 

Call to order................................... 5

 

Introductory Remarks............................ 5

 

FDA Presentation............................... 13

 

Open Public Hearing............................ 15

 

Open Committee Session......................... 26

 

Division Update................................ 26

 

Branch Updates................................. 31

 

PMA P030016

      Sponsor Presentation

      Helene Lamielle, M.D..................... 32

      Steven Slade, M.D........................ 34

      John Vukich, M.D......................... 44

      Henry Edelhauser, Ph.D................... 55

 

      Panel Questions for Sponsor.............. 69

 

      FDA Presentation

      Donna Lochner........................... 120

      Malvina Eydelman, M.D................... 128

      Gerry Gray, Ph.D........................ 138

 

Panel Questions for FDA....................... 154

 

Additional Comments from the Sponsor.......... 169

 

Committee Deliberations

      Primary Panel Reviewers

      Dr. Marian S. Macsai‑Kaplan............. 174

      Dr. Joel Sugar.......................... 187

      Dr. Michael R. Grimmett................. 192

 

Panel Discussion of PMA P030016............... 219

to Include FDA Questions to the Panel

 

 

                  C-O-N-T-E-N-T-S

 

FDA ‑ Closing Comments........................ 374

 

SPONSOR ‑ Closing Comments.................... 374

 

Voting Options Read........................... 384

 

Panel Recommendation Takes by Vote............ 422

 

Polling of Panel Votes........................ 426

 

Meeting Adjourned............................. 432

               P-R-O-C-E-E-D-I-N-G-S

                                       (8:34 a.m.)

            DR. WEISS:  Would everyone please take their seats?  We will be beginning in a moment.  I would like to call this meeting of the Ophthalmic Devices Panel to order.  We will have introductory remarks by Sally Thornton and for the record, I would like to note that there is a quorum present.

            MS. THORNTON:  Good morning. I'd like to introduce myself.  I am Sara Thornton, and I am the Executive Secretary of the Ophthalmic Devices Panel.  On behalf of the FDA, I would like to welcome you to the 106th meeting of the Ophthalmic Devices Panel.  Before we proceed with today's agenda, I have a few short announcements to make.  I'd like to remind everyone to please sign in our at the registration table.  There are sheets there for you to fill out, just your name and whether you're from industry or the panel or FDA or the public.  Please, we do like to have that filled out.

            All public handouts for today's meeting are available at the registration table.  There are two new additions to our usual group of handouts.  We've put out there information on public participation in open public hearings and copies of a guidance document for FDA and industry on quality system information for certain pre-market application reviews. 

            Messages for panel members and FDA participants, information or special needs should be directed through Ms. AnnMarie Williams, who is available at the registration table.  The phone number to call for the meeting area is 301-590-0044.  In consideration of the panel, the sponsor and the Agency we ask that those of you with cell phones and pagers either turn them off or put them on vibration mode while in this room and to make your calls outside the meeting area, please.

            Lastly, will all meeting participants please speak into the microphone and give your name clearly so the transcriber will have an accurate recording of your comments?  Now, at this time, I'd like to extend a special welcome and introduce to the public the panel and the FDA staff a new panel consultant who is with us at the table for the first time today, Dr. Oliver Schein, to my left, who comes to us from Johns Hopkins University where he holds a joint appointment as the Grossman Professor of Opthamology in the School of Medicine and as a Professor of Epidemiology in the School of Public Health and Hygiene. 

            His clinical expertise is in the medical and surgical management of patients with corneal disease and problems involving the interior segment of the eye.  I'd also like to welcome our acting industry rep, Mr. Michael Crompton, Vice President for Regulatory and Clinical Affairs and Quality Assurance for Carl Zeiss Meditec, Inc.  Mr. Crompton is sitting in for Mr. Ronald McCarley, who will not participate in today's proceedings at the request of the PMA sponsor.

            Will the remaining panel members please introduce themselves beginning with Glenda?

            MS. SUCH:  Glenda Such, Consumer Representative.

            DR. SUGAR:  Joel Sugar, University of Illinois at Chicago.

            DR. BANDEEN-ROCHE:  Karen Bandeen-Rhodes, Johns Hopkins University.

            DR. McMAHON:  Tim McMahon, Department of Ophthalmology, University of Illinois at Chicago.

            DR. MATOBA:  Alice Matoba, Cullen Eye Institute, Baylor College of Medicine.

            DR. BRADLEY:  Arthur Bradley, Professor of Vision Science, Indiana University.

            DR. WEISS:  Jayne Weiss, Kresge Eye Institute, Wayne State University, School of Medicine.

            DR. MATHERS:  Bill Mathers, Oregon Health Sciences University.

            DR. HO:  Allen Ho, Wills Eye Hospital, Philadelphia.

            DR. GRIMMETT:  Michael Grimmett, West Palm Beach Florida.

            DR. MACSAI:  Marian Macsai, Northwestern University, Chicago.

            DR. McCULLEY:  Jim McCulley, University of Texas, Southwestern Medical School, Dallas.

            DR. COLEMAN:  Anne Coleman, UCLA.

            DR. ROSENTHAL:  Ralph Rosenthal, FDA.

            MS. THORNTON:  Thank you, panel.  I'd like to read now the conflict of interest statement for this meeting of October 3rd, 2003.  The following announcement addresses conflict of interest issues associated with this meeting and is made part of the record to preclude even the appearance of an impropriety.  To determine if any conflict existed, the Agency reviewed the submitted data for this meeting and all financial interest reported by the committee participants.  The conflict of interest statutes prohibit special government employees from participating in matters that could effect their or their employer's financial interest. 

            The Agency has determined, however, that the participation of certain members and consultants, the need for whose services outweigh the potential conflict of interest involved is in the best interest of the government.  Therefore, a waiver has been granted for Dr. Oliver Schein for his interest in firms that could potentially be effected by the panel's recommendations.  The waiver which allows him to participate fully in today's deliberations involves a pending consulting relationship on a competitor's unrelated product for which he has not received any compensation and also consulting with a competitor on unrelated matters for which he receives between $10,001.00 and $50,000.00 yearly. 

            Dr. James McCulley has been granted a limited waiver which allows him to participate in the review and discussion but excludes him from voting on the application.  Dr. McCulley's waiver involves three consulting arrangements with competing firms.  For these consulting services he received greater than $50,000.00 within the past year.  Copies of these waivers may be obtained from the Agency's Freedom of Information Office, Room 12A-15 of the Park Loan Building. 

            We would like to note for the record that the Agency took into consideration other matters regarding Drs. Bradley, Schein and Coleman, Michael Grimmett, Allen Ho and Jayne Weiss.  Each of these panelists reported past or current interest involving firms at issue but in matters that are not related to today's agenda.  The Agency has determined, therefore, that the panelists may participate fully in the deliberations with the exception of Dr. McCulley, as noted previously.

            We would also like to note that the Acting Industry Representative for this meeting, Mr. Michael Crompton, reported that his employer has numerous business relationships with firms at issue.  In the event that the discussions involve any other products or firms not already on the agenda for which an FDA participant has a financial interest, the participant should excuse him or herself from such involvement and the exclusion will be noted for the record.

            With respect to all other participants, we ask in the interest of fairness that all persons making statements or presentations disclose any current or previous financial involvement with any firm whose products they may wish to comment upon.  Thank you. 

            I'd like to read not at this time the appointment to temporary voting status for this meeting.  Pursuant to the authority granted under the Medical Devices Advisory Committee Charter dated October 27th, 1990, and as amended August 18th, 1999, I appoint the following individuals as voting members of the Ophthalmic Devices Panel for this meeting on October 3rd, 2003.  Drs. William Mathers, Karen Bandeen-Roche, Joel Sugar, Marian Macsai-Kaplan and Oliver Schein.  For the record, these individuals are special government employees and consultants to this panel or other panels under the Medical Devices Advisory Committee. 

            They have undergone the customary conflict of interest review and have reviewed the materials to be considered at this meeting.  Signed, David W. Feigal, Jr. MD, MPH, Director of the Center for Devices and Radiological Health dated September 26th.  Thank you.  Dr. Weiss.

            DR. WEISS:  Thank you, Sally.  We will now begin the open public hearing.  Captain Steven Schallhorn -- I'm sorry, I'm just going to have him approach the podium and then I have a statement.  But, I'm sorry, you have a presentation to make to Dr. Matoba.  I apologize.

            DR. ROSENTHAL:  I do thank you very much.

            DR. WEISS:  That's very important.

            DR. ROSENTHAL:  I will come over and stand next to her. 

            MS. THORNTON:  Give him a microphone.  This is important. 

            DR. ROSENTHAL:  Hi.  I get two kisses this time.  I'd like to give this presentation to Alice Matoba and read the Associate Commissioner for External Relations' comments.  "Dear Dr. Matoba, I would like to express my deepest appreciation for your efforts and guidance during your term member -- your term as a member of the Ophthalmic Devices Panel of the Medical Devices Advisory Committee.  The success of this committee's work reinforces our conviction that responsible regulation of consumer products depends greatly on the experience, knowledge and various backgrounds and viewpoints that are represented on the committee. 

            In recognition of your distinguished service to the Food and Drug Administration, I am pleased to present you with the enclosed plaque".  And I am pleased to express my thanks.  Alice and I go back a long time. 

            (Applause)

            DR. MATOBA:  Well, thank you, Dr. Rosenthal.  It was a great honor for me to be asked to serve as a member of the FDA Ophthalmic Devices Panel and it's been such a great pleasure for me to work with the excellent FDA staff and fellow panel members and with you and especially with Sally Thornton, who has done such a great job.

            I have been so impressed with the thoroughness and the very high standard of scrutiny that you give to all of the protocols that we have seen and I look forward to continuing to work with you as a consultant in the future.  Thank you.

            DR. WEISS:  Thank you, Alice.  Thank you, Dr. Rosenthal.  We will now begin the Open Public Hearing but first, I wanted to read a statement that was requested by the FDA. "Both the Food and Drug Administration and the public believe in a transparent process for information gathering and decision making.  To insure such transparency of the open public hearing session of the Advisory Committee, FDA believes that it is important to understand the context of an individual's presentation.  For this reason, FDA encourages you, the open public hearing speaker, at the beginning of your written or oral statement, to advise the committee of any financial relationship that you may have with the sponsor, its product and if known, its direct competitors. 

            For example, this financial information may include the sponsor's payment of your travel, lodging or other expenses in connection with your attendance at the meeting.  Likewise, FDA encourages you at the beginning of your statement to advise the committee if you do not have such financial relationships.  If you choose not to address this issue of financial relationships at the beginning of your statement, it will not preclude you from speaking. 

            Dr. Schallhorn, we have your presentation, we have up to a half hour for the open public hearing, but you have 10 minutes at this point. 

            DR. SCHALLHORN:  Well, good morning, and thank you for allowing me to address the panel.  My name is Steve Schallhorn.  I'm an opthamologist, the Director of Cornea and Refractive Surgery at the Navy Medical Center, San Diego.  I have no financial interest in STAAR.  I'm not a paid consultant.  I've self-funded my travel to come here to address the panel.  I am a clinical investigator in the Toric ICL Study, which is ongoing but treatments at our center have not begun. 

            I'd like to also add that I'm an active duty U.S. Navy Ophthalmologist but the views that I express are not necessarily those of the U.S. Navy.

            The reason I'm here is just to address an important issue, I believe and that is that we need options.  We need surgical options, surgical options beyond what we can do with keratorefractive surgery in particular, excimer laser ablative procedures, especially to correct high myopia.  There are many issues here and they deal with issues such as thin corneas.  There are patients who are not good candidates for refractive surgery because of high refractive errors. 

            Patients with high refractive errors may not be good candidates anyway because current technology induces a number of aberrations on the cornea which can result in visual symptoms.  And there are patients or subject that we want to treat that have critical visual demands, especially those again with high refractive error.

            Now, my area of expertise and what we've studied to a great extent, deals with the quality of vision after refractive surgery and that's really what I'd like to spend the rest of the time talking about.  The -- what I'd like to talk about is a study that we've conducted looking at a 105 consecutive LASIK  subjects that we had visual acuities measurement on, questionnaires and a special test, a night-driving simulator.  I'll talk more about that. 

            This was LASIK performed with multiple laser platforms with a six and a half millimeter optical zone size with a transition zone, so it's the latest technology for high myopia.  This was also conventional and not customer wavefront-guided.  The average preop refraction was relatively high, it was minus six, a little over minus six diopters and it ranged up to minus 11.  At six months the results were good and the uncorrected visual acuity results were satisfactory with about three-quarters of the patients achieving 20/20 uncorrected.

            The night-driving simulator that we used was a derivative of the simulator that Dr. Ginsberg developed that I believe was required in some earlier investigational studies conducted for intraocular lenses.  This test, and it's shown here, you can see the -- it doesn't show up very well, but on the right side, it's looking over the shoulder of a subject in best corrected trial frames right here, looking at a rural night driving scene at 55 mile per hour.  It's done in best corrected vision.  Each eye is tested independently.  There were numerous conditions at that the subject were tested on; that was business signs, traffic signs, pedestrian hazards, et cetera. 

            Six thresholds were made for each one of those conditions for both detection and identifying what that was and it was conducted with and without a glare source simulating driving which led to 144 measurements that were made, threshold measurements, per patient and so in these 105 subjects that we tested each eye independently, with this unique test, the data represents thousands and thousands of man-hours because it's extremely labor intensive.  They're very, very specialized tests, but nonetheless, it's a performance-based task and that's what I'm going to start with.

            It is a performance-based task, whereas, other tests, I should say of visual acuity such as contrast sensitivity, you can ask yourself, I certainly pondered this, you know, what does it mean if somebody has a subtle loss of contrast?  What does that really mean and that's a very good question?  What does that really mean and we're trying to get an answer to that, what does that really mean, but a performance based task built in has some of those answers addressed.  This is a task that we are now looking at.

            We look at that.  Under all conditions, in this population of 105 subjects, we find a decrement in night driving performance.  How much of a decrement?  A little bit.  This is the data shown another way and this shows the seconds improvement or the seconds decreased in the detection or identification distance, preop to post-op, so it's a paired analysis and zero represents no change post-op compared to preop and you can see most patients had no change.  But the trend and the significant -- and it is significant that there was a loss.  About 40 percent of patients had one second or longer increase in their detection distance. 

            Now, you could ask also, what does one second mean?  Is that significant?  We've worked with the National Traffic Safety Administration on the meaning of this and they've conducted studies which have shown that one second is a significant decrement  in night driving performance at 55 miles per hour under similar but different circumstances.  So it's a  -- we're seeing a significant loss in a significant portion of patients treated with LASIK for relatively high levels of myopia. 

            Now, let's look at the vision.  This is best corrected and five percent contrast acuity shown on the same chart.  In orange, it's best corrected and this is lines gained or lost and you can see most patients had no change but the curve has shifted to the right meaning more patients had improvement than a decrement, consistent with what we see and that's, perhaps, partly due to reduction in minification from the act of putting that correction on the cornea.

            In contrast to what we see with high contrast acuity, we see a shift to the left or worse with five percent contrast acuity, five percent low contrast acuity.  It's an ETDRS eye chart, that five percent level and it's backlit.  We see a loss, in fact, 25 percent of patients having measurable loss of contrast acuity with this.  How about the symptomatology, most patients have no change in their symptomatology, preop to post-op.  However, the curve is shifted slighted toward worse.  Again, this is a paired analysis.  We're looking at all patients and the difference between post-op and preop.  It's slightly shifted worse, meaning patients have symptoms.  In fact, a subset of patients can have relatively significant symptoms after the surgery. 

            Now, we tried to find out, okay, what are the factors that now are related to their driving performance decrement, what are those factors and we've done correlation analysis.  And we find surprisingly that pupil size placed no factor whatsoever and I'll talk more about the briefly.  Pupil size placed no factor in their night driving performance.  Where we see a significant decrement pupil size has no effect.  One of the strongest effects we see, though, is the level of preop myopia.  The higher level of preop myopia, the worse the night driving symptoms.  I'll talk, again, more about that.

            We also get correlations with symptomatology in night driving performance.  We get correlations with the contrast.  People who have worse contrast, don't do as well in night driving.  That all makes sense.  Here's, just quickly, shows the low-light pupil diameter and you can see we had patients that were eight millimeters or larger.  We had a wide range of pupils.  We did not exclude patients who had large pupils in this study.  Just to repeat, we did not exclude patients who had large pupils from the study.  We had a broad distribution of pupil size.  We found no correlation with pupil size.

            And all of the analysis that we've done, other types of analysis with many, many other data sets have shown no correlation with pupil size.  However, we do find a significant correlation again, as I mentioned, with preop myopia.  Patients who have high levels of preop myopia had a significant decrease in the night-driving performance.  You can see on a scatter plot of all the data that there is significant spread.  However, there is a significant relationship also.

            Now, what are the causes of this, what are the causes of these problems after LASIK and the answer is, I think, has to do with higher order aberrations, the induction of higher order aberrations.  This is looking at preop, a distribution of the higher order RMS preop and looking at it post-op in yellow and we see a significant increase in the higher order aberrations. 

            We do correlation analysis with those higher order aberrations and we find that the level of preop myopia is significantly correlated to induced or an increase in spherical aberration.  And again, a lot of scatter, but a significant relationship.  Likewise, we find that increase in higher order aberrations, higher order RMS, change in higher order RMS vertically versus change in five-percent contrast horizontally that there also a significant relationship.  Patients who have increase in higher order aberrations have an increase or a decrease in their contrast acuity. 

            Anyway, in conclusion, conventional LASIK works well.  Most patients have no symptoms, but in some patients, it can induce visual symptoms, it can reduce low contrast acuity, it can increase higher order aberrations and it can decrease night driving visual performance.   Preop myopia is the strongest risk factor.  Patients who are especially above six diopters have the greatest risk and, of course, that's also the range where improved algorithms, improved ways to do LASIK, such as wavefront-guided surgery, is not yet -- is not available. 

            And lastly, we need these kind of surgical options.  Surgical options are needed especially to correct higher orders of myopia.  Thank you.

            DR. WEISS:  Thank you, Dr. Schallhorn.

            (Applause)

            DR. WEISS:  We don't usually have questions at this point, but if anyone had any pressing questions for Dr. Schallhorn, we could limit them to a few, otherwise, we'll -- Dr. Bradley does, Dr. Schallhorn.

            DR. BRADLEY:  Thanks for the presentation, Dr. Schallhorn.  One question, you made an emphatic statement that pupil size was not critical.  You then inferred from your data that these driving problems were related to higher order aberrations.  Well, the one thing we know for use is that as pupil size gets bigger, aberrations get worse.  So how can there be a correlation with higher order aberrations but not with pupil size?

            DR. SCHALLHORN:  Well, aberrations can increase as the pupil size increases.  But its effect on visual performance is what I'm saying we don't see that effect on visual performance.  For instance, there may be -- I think there are things we really don't understand about the visual system and this comes to the heart of several of them.  You can have a very aberrated eye that might have aberrations at seven or eight millimeters but it may not effect visual performance.  You can measure it on an aberrometer, but if it doesn't effect visual performance, I'm not sure. 

            You know, I think the central four, five, six maybe larger than that, millimeters, of the visual system is critical for high quality vision but it may not be that the eye has to be that perfect beyond that range, even though we can measure aberrations in that range.

            DR. WEISS:  Thank you very much.  We are going to move onto the open committee session with the Division update by Dr. Rosenthal, followed by a Branch update by Donna Lochner.

            DR. ROSENTHAL:  Thank you, Dr. Weiss.  This year we are pleased to announce the addition of several members to the staff of our Division and I'd like to introduce them to you.  There are actually two from the Ear, Nose and Throat Branch but I will not introduce them.  They're not here and probably will not be playing much of a role, though I will comment on them at the end on their -- who they are.

            First, I'd like to introduce Lori Austin-Hanberry, who has joined our Division in the position of Project Manager.  Amongst her duties will be insuring that the Division meets MDUFA (ph) product review goals.  She's a Lieutenant Commander in the Public Health Service, has over 14 years experience as a registered nurse with clinical, instructional and management background.  Prior to joining FDA she managed various clinical and administrative operations for the Montgomery County Department of Health and Human Services, most recently managing the Childhood Lead Poisoning and Prevention Program.

            She was also a Captain in the Air Force Reserves for 11 years.  She obtained her nursing degree from Howard University and her Masters Degree in Health Care Administration from Central Michigan University.  Lori?