UNITED STATES OF
AMERICA
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FOOD AND DRUG
ADMINISTRATION
MEDICAL DEVICES ADVISORY
COMMITTEE
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OPHTHALMIC DEVICES
ADVISORY PANEL
106TH
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?