U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES

FOOD AND DRUG ADMINISTRATION

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CENTER FOR DEVICES AND RADIOLOGICAL HEALTH

MEDICAL DEVICES ADVISORY COMMITTEE

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OPHTHALMIC DEVICES PANEL

105^TH^ MEETING

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FRIDAY

MAY 23, 2003

The Meeting was convened in Salons A, B, and C of the Gaithersburg
Marriott, 9751 Washingtonian Boulevard, Gaithersburg, Maryland, at 8:30
a.m., Dr. Jayne S. Weiss, Chair, presiding.

[PRESENT:]{.underline}

JAYNE S. WEISS, MD Chair

SARA M. THORNTON Executive Secretary

ARTHUR BRADLEY, PhD Voting Member

MICHAEL R. GRIMMETT, MD Voting Member

ALICE Y. MATOBA, MD Voting Member

TIMOTHY T. McMAHON, OD Voting Member

ALLEN C. HO, MD Voting Member

ANNE L. COLEMAN, MD, PhD Voting Member

TERRI L. YOUNG, MD Consultant,

deputized to vote

GLENDA V. SUCH, MEd Consumer Representative

RONALD E. McCARLEY Industry Representative

[FDA PARTICIPANTS:]{.underline}

A. RALPH ROSENTHAL

JAN C. CALLAWAY

JAMES F. SAVIOLA, OD

DONNA R. LOCHNER

BERNARD P. LEPRI, OD, MS, MEd

DON CALOGERO

A-G-E-N-D-A

**OPEN SESSION**

Call to Order, Jayne S. Weiss, M.D., Chair 5

Introductory Remarks, Sara M. Thornton, Executive Secretary 5

Conflict of Interest Statement 8

Appointment to Temporary Voting Status 10

**OPEN PUBLIC HEARING** 11

**OPEN COMMITTEE SESSION**

**DIVISION UPDATE**

A. Ralph Rosenthal, M.D., Director, Division

of Ophthalmic and Ear, Nose and Throat

Devices 13

**BRANCH UPDATES**

James F. Saviola, O.D., Chief, Vitreoretinal and Extraocular Devices
Branch 14

Jan C. Callaway, Acting Chief, Diagnostic and Surgical Devices Branch 19

Donna R. Lochner, Chief, Intraocular and Corneal Implants Branch 20

**PMA PO30002** - **SPONSOR PRESENTATION**

CrystaLens Model AT-45, Multipiece Silicone Posterior Chamber
Accommodating Intraocular Lens 21

Panel Questions for the Sponsor 60

**FDA PRESENTATION**

Donna R. Lochner - Introduction 90

Bernard L. Lepri, O.D., M.S., M.Ed. - Clinical Reviewer 92

Additional Comments from the Sponsor 97

**COMMITTEE DELIBERATIONS**

Primary Panel Reviewers:

Anne L. Coleman, M.D., Ph.D. 100

Arthur Bradley, Ph.D. 105

PANEL DISCUSSION OF PO30002 to include FDA questions to the Panel 128

30-MINUTE OPEN PUBLIC HEARING SESSION 231

FDA - CLOSING COMMENTS 231

SPONSOR - CLOSING COMMENTS 232

Voting Options Read 238

PANEL RECOMMENDATION TAKEN BY VOTE 240

POLLING OF PANEL VOTES 252

COMMENTS FROM CONSUMER AND INDUSTRY

REPRESENTATIVES 256

FINAL PANEL COMMENTS 257

ADJOURN

P-R-O-C-E-E-D-I-N-G-S

8:30 a.m.

CHAIRPERSON WEISS: I would ask all the panel members to be seated,
please. I would like to call this meeting of the Ophthalmic Devices
Panel to order and we will have introductory remarks by Sally Thornton.

EXECUTIVE SECRETARY THORNTON: Good morning. Permit me to introduce
myself. I am Sara Thornton, otherwise known as Sally, the Executive
Secretary of the Ophthalmic Devices Panel. On behalf of the FDA I would
like to welcome you to the 105th meeting of the panel.

Before we proceed with today\'s agenda I have a few short announcements.
I would like to remind everyone to sign in on the attendance sheets in
the registration area just outside the meeting room. All public handouts
for today\'s meeting are available at that table.

If you have any messages for panel members and FDA participants,
information, or special needs, they should be directed through Ms. Anne
Marie Williams, who is sitting by the door there, who is available in
the registration area also. The phone number for calls to 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.

Lastly, will all meeting participants please speak into the microphone
and give your name clearly so the transcriber will have an accurate
record of your comments.

Now, at this time I would 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.

Dr. Terri Young, who is seated to my left, who comes to us from
Philadelphia, Pennsylvania, where she is an Associate Professor of
Ophthalmology and Pediatrics and Director of the Ophthalmic Genetics
Research Laboratory and Ophthalmic Genetics Clinic at the University of
Pennsylvania\'s Children\'s Hospital.

Welcome to our table, Terri.

Will the remaining panel members please introduce themselves beginning
with Mr. Rick McCarley.

MR. McCARLEY: I\'m Rick McCarley, President of Ophtec, and I\'m the
industry representative.

DR. GRIMMETT: I\'m Michael Grimmett, Assistant Professor of Bascom
Palmer Eye Institute in Miami, Florida.

DR. McMAHON: I\'m Tim McMahon, Professor of Ophthalmology at the
University of Illinois in Chicago.

MS. SUCH: I\'m Glenda Such, Lighthouse International, New York City.

CHAIRPERSON WEISS: Jayne Weiss, Professor of Ophthalmology and
Pathology, Kresge Eye Institute, Wayne State University, Detroit
Michigan.

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

DR. MATOBA: Alice Matoba. I\'m Associate Professor of Ophthalmology,
Baylor College of Medicine, Houston, Texas.

DR. HO: Allen Ho, Associate Professor at Wills Eye Hospital.

DR. COLEMAN: Anne Coleman, Associate Professor of Ophthalmology at UCLA
in Los Angeles.

DR. ROSENTHAL: Ralph Rosenthal, Division Director, FDA.

EXECUTIVE SECRETARY THORNTON: Now I would like to read the conflict of
interest statement.

The following announcement addresses conflict of interest issues
associated with this meeting and is made a part of the record to
preclude even the appearance of an impropriety.

To determine if any conflict existed the agency reviewed the submitted
agenda 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
affect their or their employer\'s financial interest.

However, the agency has determined that 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 under 18 USC 208(b)(3) has been granted to Dr. Jayne
Weiss for her consulting with the competitor\'s unrelated product. We
receives less than \$10,001 a year. The waiver allows this individual to
participate fully in today\'s deliberations. Copies of this waiver may
be obtained by submitting a written request to the agency\'s Freedom of
Information Office, Room 12A-15 of the Parklawn Building.

We would like to note for the record that the agency took into
consideration certain matters regarding Drs. Anne Coleman, Allen Ho,
Michael Grimmett, Jayne Weiss, and Terri Young. These panelists reported
current and/or past interest in firms at issue but in matters that are
not related to today\'s agenda. The agency has determined, therefore,
that they may participate fully in the panel\'s deliberations.

We would also like to note for the record that Mr. Ronald McCarley, who
is industry representative at this meeting, is the president of a firm
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
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.

I would like now to read the appointment to temporary voting status.
Pursuant to the authority granted under the Medical Devices Advisory
Committee charter dated October 27, 1990, and as amended August 18,
1999, I appoint the following individual as a voting member of the
Ophthalmic Devices Panel for this meeting on May 23, 2003, Terri L.
Young, M.D.

For the record, this individual is a special Government employment and
consultant to this panel or other panels under the Medical Devices
Advisory Committee. She has undergone the customary conflict of interest
review and has reviewed the material to be considered at this meeting.
Signed, David W. Feigel, Jr., M.D., M.P.H., Director for the Center for
Devices and Radiological Health dated May 13, 2003.

Thank you, Jayne.

CHAIRPERSON WEISS: Thank you, Sally.

The open public hearing portion of this meeting will now begin. Any
speaker who wishes to make a presentation before the committee is doing
so in response to the panel meeting announcement in the Federal
Register. They are not invited to speak by the FDA, nor are their
comments, data, or products endorsed by the agency.

Scheduled speakers are given a 10-minute limit. I will recognize
unscheduled speaker as time allows. Those who wish to speak are asked to
state for the record their association with the sponsor or sponsors of
any product being considered by the panel at this meeting whether you
are an investigator or consultant, study subject, etc.

Please state whether you are receiving reimbursement from any device
firm for your presentation, transportation, or other expenses to appear
at this meeting. Lastly, you will need to state if your organization
receives funding from a sponsor whose product is being considered or
from a sponsor of a competing product.

I may ask the speaker to remain at the podium if the panel members wish
to question them further. Only members of the panel may question
speakers during the open public hearing. Is there anyone who is going to
be coming to the podium for this?

EXECUTIVE SECRETARY THORNTON: There have been no scheduled speakers.

CHAIRPERSON WEISS: Seeing no speakers, we will now close the open public
hearing and move on to the open committee session beginning with the FDA
division update.

DR. ROSENTHAL: I just wanted to make a couple comments. After many years
of not being able to hire anybody, we have been given leave to hire
people for the division because of the new Medical Device User Fee Act.
We will be searching for individuals to come and work for the FDA. If
anyone has anyone that might be interested, we\'d be delighted to hear
from them.

The other thing is Dr. Saviola said he wasn\'t going to give an update
on this issue but I just read in the American Academy of Ophthalmology
Washington Report which is a public document that Congress has
introduced the Plano Lens Bill.

The bill was introduced by Representative Henry Waxman and
Representative John Bosman that amends the Federal Food, Drug, and
Cosmetic Act to recognize and regulate both corrective and
non-corrective contact lenses as medical devices regardless of their
intended use. Thank you.

CHAIRPERSON WEISS: Thank you very much, Dr. Rosenthal.

Dr. Saviola.

DR. SAVIOLA: Good morning. I intend to update on FDA matters. That\'s
why I deferred to Ralph that last note.

In the Federal Register of April 4, 2003, FDA published a Notice of
Availability for guidance to FDA staff on sampling or detention without
physical examination of decorative contact lenses.

The document includes FDA\'s guidance to FDA district offices for
sampling or detention without physical exam of Plano zero-powered
non-corrective contact lenses that are intended solely to change the
appearance of the normal line of decorative fashion when these products
are presented for importation to the United States.

Section 201(i) of the Food, Drug, and Cosmetic Act defines cosmetic to
include articles intended to be rubbed, poured, sprinkled, or sprayed
on, introduced into, or otherwise applied to the human body or any part
thereof for cleansing, beautifying, promoting attractiveness, or
altering the appearance.

Decorative contact lenses are articles intended to be introduced into
the eye which is part of the body to beautify the wearer, promote the
attractiveness of the wearer, or alter the wearer\'s appearance.

Their claim to achieve their cosmetic result by changing the apparent
color of the iris by appearing to add a design to the iris. For example,
a professional sports team insignia, or by imparting a non-human or
otherwise non-normal appearance to the eye like a cat\'s eye.

Provided they are not marketed with claims that they affect the physical
or physiological change to the eye, decorative contact lenses are
properly regulated as cosmetics under the act. The courts have read
statutory definitions employing the term \"intended\" to refer to
specific marketing representations.

The fact that contact lenses are devices in the colloquial sense does
not preclude cosmetic status under the act. FDA has previously
determined that Section 201(i) of the Act applies to appearance
enhancing devices. Also the fact that a product is intended to come into
contact with the eye does not make it ineligible for cosmetic
regulation.

On October 22, 2002, FDA issued an import alert with respect to
decorative contact lenses. The revised import alert, as noted in the
Federal Register, does not cover contact lenses that are intended for
vision correction or for prosthetic or other medical use.

There are some lenses currently on the market under 510(k) covering
contact lenses intended for both vision correction and decorative
purposes. The sponsors in these cases voluntarily included a Plano Lens
in the power range of the corrective powers described in the 510(k)
submission.

These products are regulated by FDA as medical devices under the act.
Such control is not available for decorative contact lenses because
these products are cosmetics under the act.

Section 801(a) of the Act authorizes FDA to refuse admission of articles
that appear to be adulterated or misbranded. The guidance represents the
agency\'s current thinking on the sampling or detention without physical
exam for decorative lenses that appear to be adulterated or appear to be
misbranded. Please read the Federal Register notice for more detailed
discussions of adulteration or misbranding of these products.

I have prepared \-- out on the table there\'s a piece of paper, I think
it\'s in your packets, which has all the different websites that are
pertinent to that discussion.

I just want to comment that FDA has taken a very strong position that it
is necessary to have involvement of an eye care provider to fit and
follow soft Plano Lens wearers to better manage risks associated with
their use.

This position is described in a press release that warned consumers
about the risk of permanent eye injury and even blindness associated
with decorative contact lenses distributed without a prescription and
without proper fitting by an eye care professional.

The center also issued a public health web notification directed at
health professionals that noted the significant risk of blindness and
other eye injuries if non-corrective or cosmetic lenses are distributed
without an eye care professional\'s involvement.

Also an article appeared in the FDA consumer magazine. The press release
web notification professionals and consumer articles information on how
to report problems to the FDA under the Medwatch program.

The FDA Medwatch database subsequently recorded over 10 reports of
decorative or colored contact lens events since the warnings last fall.
This may not seem like many but the total for previous years combined
was equal in a few month\'s time. I would like to encourage all eye care
professionals to document cases of contact lens related injuries via the
Medwatch program.

Until the update that Dr. Rosenthal gave on the legislation passes,
that\'s the way things are handled right now, that those lenses are
going to be regulated as cosmetics. Thank you.

CHAIRPERSON WEISS: Thank you.

Jan Callaway.

MS. CALLAWAY: Good morning. We have had two PMA approved devices since
the last panel update of August 2002. On October 28, 2002, we approved
P970043, Supplement 10, for the Alcon LADARVision 4000 Custom Cornea
indicated for wavefront-guided Lasik for the reduction or elimination of
myopia up to seven diopters with less than .5 diopters of astigmatism at
the spectacle plane.

On February 25, 2003, we approved P990027, Supplement 4, for the Bausch
& Lomb TECHNOLAS 217A Excimer Laser System indicated for lasik
treatments for the reduction or elimination of low to moderate naturally
occurring hyperopia of 1 to 4 diopters with or without refractive
astigmatism up to 2 diopters.

Since August 2002 we have cleared approximately 30 510(k)\'s. On January
1, 2003, we lost the services of Gwen Hong, an engineer and team leader
in DSDB who transferred to the Office of Surveillance and Biometrics in
the Center for Devices and Radiological Health.

In April 2003 we sent a form letter to all IDE sponsors suggesting that
even if they had a previous PMA approval they should meet with us prior
to submitting their PMA.

This pre-PMA meeting will provide an opportunity to pass along
information regarding appropriate endpoints, stability information,
safety and effectiveness tables, and formatting for labeling of the PMA
with the hopeful result being a more manageable PMA for both FDA and the
sponsor with fewer deficiencies identified during FDA review. Thank you.

CHAIRPERSON WEISS: Thank you.

Donna Lochner.

MS. LOCHNER: P010059 is the premarket approval application for Morcher
GmbH and capsular tension ring used for capsular bag stabilization in
patients with pseudoexfoliation syndrome or other situations of
compromised zonulars.

This PMA was reviewed by the Ophthalmic Devices Panel in January of
2002. The panel recommended that the PMA was approvable with request for
essentially a complete reanalysis of the clinical data to resolve
discrepancies in the PMA and to clarify information presented at the
panel meeting.

At this time the PMA has not yet been approved. We are currently working
with the sponsor to resolve the remaining issues. Thank you.

CHAIRPERSON WEISS: Thank you for that update. We will now go on to the
sponsor presentation. I would like to move to the review of PMA P030002
and invite the first presenter to come to the podium.

The sponsor has one hour. I would like each presenter to identify
themselves and I will remind you to identify any financial interest that
you may have at the beginning of the presentation.

MR. KRAMSKY: Good morning. My name is Paul Kramsky. I\'m Vice President
of Regulatory Affairs and Quality Systems for C&C Vision. We are pleased
to present to you today PMA P030002 for the CrystaLens silicone
posterior chamber accommodating intraocular lens for implantation of
patients with cataracts.

Presenting on behalf of C&C Vision today will be Dr. Michael Breen from
our clinical staff, and Dr. Stephen Slade, Michael Colvard, and Adrian
Glasser, all of whom are consultants and have a financial interest in
C&C Vision. Dr. Judy Gordon, a clinical regulatory consultant for C&C
Vision will facilitate discussions.

The CrystaLens has the same indications for use as any standard
intraocular lens that is intended for primary implantation for the
visual correction of aphakia in adult patients with cataracts.

Additionally, the CrystaLens provides patients with improved vision at
near, intermediate, and distance without spectacles as will be
established in our presentation of the clinical trial conducted in
support of this PMA.

The first presentation this morning will be made by Dr. Michael Breen,
Director of Clinical Outcomes for C&C Vision.

DR. BREEN: Good morning. My name is Dr. Michael Breen and I will review
the developmental history of the CrystaLens, the product specifications,
and the proposed mechanism of action.

Since this is the first accommodating IOL to be reviewed by this panel,
we would like to start with the definition of accommodation. While a
review of the published literature on this subject provides a number of
definitions and descriptions of accommodation, we believe the best
description defines what is ultimately important to the

patient - the ability of the eye to change focus and to afford the
patient a clear image over a range of distances.

Generally, monofocal IOLs have been used to provide the postoperative
cataract patient with functional distance vision. Patients usually
require a correction for intermediate and near vision. Consequently,
there has been a great deal of interest in finding treatment modalities
that can provide postoperative cataract patients with intermediate and
near vision in addition to distance vision.

A number of options for providing near vision in pseudophake patients
has been evaluated with varying degrees of success including monovision,
implantation of multifocal and bifocal intraocular lenses which are
available commercially, and now an accommodating intraocular lens which
is the subject of our presentation.

The premise for the development of an intraocular lens that can
accommodate as suggested by a body of published literature, Fisher
established that the ciliary muscle maintains functional activity with
age. This was confirmed by Strenk and Colleagues using magnetic
resonance imaging, or MRI, to show that the ciliary muscle retains much
of its contractility in older patients.

In clinical practice Cumming showed that plate lenses fall against the
vitreous face and further observed that in some patients implanted with
plate lenses the optic may move forward following pilocarpine
administration.

Coleman\'s observations in primate eyes that electrical stimulation of
the ciliary muscle results in accommodation with an accompanying
increase in vitreous cavity pressure and a simultaneous decrease in
anterior chamber pressure suggest the basis for the experience of
Cumming and other surgeons using plate lenses.

Taken together, these findings suggest that an appropriately designed
intraocular lens might have the ability to move along the axis of the
eye as a result of pressure changes between the anterior chamber and the
vitreous cavity leading to the development of the CrystaLens.

The CrystaLens is a modified plate haptic lens with a biconvex optic.
The optic material was a third generation silicone with a refractive
index of 1.43 and a UV filter. The plate length is 10.5 millimeters. The
overall length of the lens measures 11.5 millimeters and the optic
diameter is 4.5 millimeters.

The lens has hinges adjacent to the optic allowing forward and backward
movement of the lens along the axis of the eye. The polyamide loop
provides fixation, centration, and stability of the lens in the capsular
bag.

This slide summarizes the proposed mechanism of action of the
CrystaLens. As previously mentioned, studies by Busaka and Strenk, et
al., suggest that the ciliary muscle contraction in relaxation results
in the redistribution of muscle mass.

Further, Strenk, et al., showed that active ciliary muscle contraction
still occurs with an accommodative effort in subjects up to 83 years
old. In 1986 Coleman showed a differential pressure increase in the
vitreous cavity with accommodation in primates.

The CrystaLens is designed to take advantage of vitreous cavity pressure
changes by locating against the vitreous face. This allows the lens
optic to move forward and backward in response to ciliary muscle
contraction and relaxation and altering pressure changes between the
vitreous cavity and the anterior chamber. The hinged haptics facilitate
axial movement of the CrystaLens by minimizing resistance.

This image of an eye implanted with the CrystaLens one day after surgery
was captured with Scheimpflug technology. This shows the desired
posterior position against the vitreous.

Development of the CrystaLens was conducted according to FDA guidance in
ISO standards protesting of intraocular lenses with additional testing
performed to address the specific characteristics of the lens. This
testing included biocompatibility, effective YAG laser in vitro,
hydrolytic stability, photostability, and exhausted extraction.

Optical and mechanical testing was also performed and included dynamic
fatigue testing to establish the durability of the hinge. All testing
was successfully completed and was submitted to the FDA initially as
part of the IDE application and also as part of this PMA.

Now it is my pleasure to introduce Dr. Stephen Slade who will present
the study design and the visual acuity outcomes.

DR. SLADE: Thank you, Michael. Good morning. I\'m Steve Slade,
investigator and medical monitor for the C&C Vision CrystaLens
Accommodating IOL Study. I do have a financial interest in C&C Vision.

It\'s my pleasure to present to you the study design and visual acuity
results from this perspective multi-center clinical investigation. We
had 14 U.S. clinical investigators and three non-US sites contributing
to this clinical trial.

The clinical trial for the CrystaLens was conducted under an FDA
approved IDE and was designed according to FDA guidance for intraocular
lenses and draft guidance for multifocal intraocular lenses. Subjects
were required to be at least 50 years of age with cataracts.

Potential for best corrected visual acuity of 20/32 or better was
required. Eyes with more than a diopter of corneal astigmatism were
excluded from participation. Follow-up exams were conducted at
traditionally accepted intervals over the course of our one-year study.

Multiple measures of near, intermediate, and distance visual acuity were
performed on the entire study population. However, as defined in the IDE
study protocol, the primary measure of accommodative functionality of
the CrystaLens was near vision measured through the patient\'s distance
correction obtained by manifest refraction.

By measuring near vision through the patient\'s distance correction, we
eliminated residual myopia and astigmatism which can contribute to
functional near vision. Uncorrected near vision was measured as well.
Intermediate visual acuity was measured both through the distance
correction and without correction for our bilaterally implanted
subjects.

Finally, both uncorrected and best corrected distance visual acuity were
measured for all study eyes. Monocular visual acuities will be shown for
the primary eyes, first implanted in each subject, and monocular visual
acuities are shown for our subject bilaterally implanted subjects.
Unless otherwise indicated, visual acuities are presented for the
one-year follow-up.

Standardized methods and equipment were used for all measurements of
visual acuity at all U.S. clinical sites with rigorous control of
lighting and chart distances. Distance visual acuity was measured using
the Stereo Optical Optec X1600 equipped with an ETDRS acuity chart and
luminance of 85 cd/m2.

These units were calibrated for a 20-foot or six meter testing distance.
Near an intermediate acuity were measured using MNREAD acuity chart
shown here also using a luminance of 85 cd/m2.

This is a logMAR chart with text rather than individual optotypes and
is, therefore, considered a test of functional vision. Near visual
acuity was tested at 16 inches or 40 centimeters. Intermediate visual
acuity was tested at 32 inches or 80 centimeters.

Testing distances were kept constant from site to site, patient to
patient, by fitting the charts with a nylon cord that was marked at 16
and 32 inches.

Testing distances were verified prior to each intermediate and near
visual acuity measurement. The lighting in each exam room at every site
was calibrated frequently during the course of the study to ensure the
luminance required remained constant for all patient examinations.

A total of 497 eyes of 324 subjects were implanted with the CrystaLens
at the 17 clinical sites. Consistent with other trials of intraocular
lenses there were more females enrolled than males and the mean age of
the study patients was 69.7 years.

The study cohort of 497 eyes represents 324 primary eyes and 173 fellow
eyes. Per FDA guidance for clinical trials of intraocular lenses,
analysis of safety and effectiveness are based on the primary eyes
rather than the total eyes implanted, although complete data on all
implanted eyes were provided in our PMA submission. During our
presentation visual acuity measured binocularly will be shown for the
bilaterally implanted subjects.

The safety cohort consisted of all 324 eyes while the effectiveness
cohort consisted of 263 eyes implanted and followed at the U.S. clinical
sites. Eyes implanted at the non-U.S. sites are not included in the
effectiveness cohort since nonstandardized charts were used as MNREAD
charts are not available in languages required, specifically French and
Portuguese. Accountability for the effectiveness and safety cohorts at
one year was over 93 percent.

I\'ll be presenting outcomes for measurement of near, intermediate, and
distance visual acuity follow-up. As I have already mentioned, monocular
visual acuities are shown for the primary eyes, first eye implanted in
each subject. Monocular visual acuities are shown for our subset of
bilaterally implanted subjects.

This is the MNREAD chart which I have shown you. Here we have outlined
the 20/40 line. We all talk about visual charts. We all spend
considerable time in sharing standardization. For this presentation,
though, we wanted to go a step further and try to highlight what our
results really mean to patients in day-to-day settings.

20/40 line corresponding to 6 point font is shown here. The MNREAD
charts, again, require patients to read text as a measure of functional
vision in contrast to charts that show single optotypes.

Keeping the same 20/40 text centrally on the screen, we would like to
show you an important example of a real life near vision reading
situation, an Advil bottle with 20/40, or 6 point font.

As we go through the visual acuity data results for the study
population, we hope this will help illustrate the accommodated benefits
provided by the CrystaLens, especially considering 93.8 percent of our
bilaterally implanted subjects had uncorrected near visual acuity of
20/32 or better at one year.

Now, uncorrected near visual acuity is displayed on this slide for the
total cohort of 241 primary eyes. Binocular uncorrected visual acuity
was available at one year for 124 of our 127 bilaterally implanted
subjects.

88.4 percent of primary eyes and 98.4 percent of the bilaterally
implanted subjects achieved uncorrected near visual acuity of 20/40 of
better. 93.5 percent of the bilaterally implanted subjects achieved
20/32 or better, near visual acuity through the distance correction.

Near vision was also measured through the subject\'s distance correction
obtained by manifest refraction. By measuring near vision through the
distance correction we eliminated residual myopia and astigmatism which
can contribute to functional near vision.

90.1 percent of the primary eyes achieved distance corrected near visual
acuity of 20/40 or better while 100 percent of the subjects implanted
bilaterally achieved distance corrected near visual acuity of 20/40 or
better.

Now, while accommodated functionality in the study population is
established by measuring near and intermediate visual acuity through the
distance correction to eliminate myopia and astigmatism as confounders,
what the patient really wants is a full range of vision without
spectacles including uncorrected near vision.

This slide shows monocular near acuity for eyes with postoperative
refractions within a half a diopter of plano set for distance to
eliminate those eyes with postoperative refractive errors of myopia and
hyperopia. This represents 163 of our primary eyes, 243. 89.6 percent of
these eyes with good distance refractive outcomes achieved uncorrected
near acuity of 20/40 or better which corresponds to J3 on the familiar
Jager chart.

Intermediate visual acuity measured through the distance correction for
primary eyes and for bilateral implants subjects also is excellent. 95
percent of our primary eyes and 100 percent of the bilateral implants
subjects achieved an intermediate visual acuity of 20/25 or better
through their distance correction. Additionally, 98.4 percent of the
bilateral implanted subjects achieved an uncorrected intermediate acuity
of 20/25 of better.

The results for uncorrected distance visual acuity for primary eyes and
bilateral implanted subjects at one year are combined on this slide.
88.9 percent of the primary eyes corrected distance visual acuity of
20/40 or better.

The percentage of bilaterally implanted eyes in blue achieving
uncorrected distance visual acuity of 20/25 or better was 91.9 percent
with 97.6 percent achieving 20/32 or better and 98.4 achieving 20/40 or
better.

Uncorrected distance acuity for eyes with a good refractive outcome
postoperatively within half a diopter was also excellent with 97 percent
of eyes with this refractory outcome achieving an uncorrected distance
acuity of 20/40 or better and 86.7 percent of these eyes at 20/25 or
better.

The safety of this lens was also very good with 96.7 percent of primary
eyes and 100 percent of bilateral implanted subjects correctable
postoperatively to 20/25 or better. A key measure of the function of an
accommodating intraocular lens is whether the same eye or the same
subject achieved both near and distance visual acuity, uncorrected and
distance corrected.

78.8 percent of our primary eyes had both uncorrected near and distance
visual acuity of 20/40 or better. While in our bilaterally implanted
subjects, 96.7 percent achieved uncorrected visual acuity of 20/40 or
better at both distance and near.

To further substantiate functionality of an accommodating IOL the
confounding myopia and astigmatism should be eliminated by measuring
acuity to the distance correction. 89.6 percent of our primary eyes and
100 percent of our bilaterally implanted subjects had both near and
distance acuity of 20/40 or better through their distance correct.

We would like to present further key study findings including the
effective biometry method on the visual acuity, the effect of the
subject age on the near visual acuity, effective YAG capsulotomy on near
acuity, the stability of the near visual acuity over time, and the
stability of the manifest refraction over time.

To evaluate the effect of biometry, we compared uncorrected near visual
acuity from non-immersion versus immersion methods. While biometry had
only a limited impact on uncorrected near acuity at the 20/40 level, a
significantly larger portion of eyes achieved uncorrected near acuity of
20/32 or better when immersion biometry was used.

Similarly, use of immersion biometry resulted in a larger proportion of
eyes with uncorrected distance acuity of 20/32 or better. But the
outcomes were generally good regardless of the method used.

Did younger subjects have better outcomes than older subjects? When we
stratified our cohort by age and decades there were no statistically
significant differences in outcomes suggesting an equally good
accommodated functionality even in the older study subjects.

Could capsular fibrosis interfere with lens functionality? In fact,
distance corrected near acuity was generally unchanged from the early
postoperative period through 11 to 15 months in blue. These data address
concerns that the natural course of capsular fibrosis may reduce the
accommodative ability of the lens over time.

The stability of near visual acuity through the distance correction is
further confirmed by looking at changes in lines of vision over time.
Overall 79 percent \-- 79.8 percent of the eyes remained within one line
across the study visits shown.

Did a YAG capsulotomy affect the functionality of the lens? We compared
near vision through the distance correction for eyes that had YAG
capsulotomy to non-YAG with documented clear posterior capsules. Eyes
with any trace of posterior capsular haze were excluded from the non-YAG
group.

There was no difference in distance corrected near visual acuity for
eyes that had undergone YAG laser capsulotomy as compared to the non-YAG
population of eyes. It should be noted there were no specific criteria
in the study for performing YAG capsulotomy and the pre-YAG best
corrected distance visual acuity was 20/25 or better and 30 of the 34
YAG eyes. Draft labeling for the CrystaLens recommends limiting the size
of the YAG capsulotomy to no more than 4 millimeters.

Another question was raised in regard to stability of the hinge. To
address this we looked for change in manifest refractive spherical
equivalence stability over time in a consistent cohort of primary eyes.
In fact, refractive stability was very good. 85 percent of eyes changing
by a half a diopter or less and 96.6 percent of eyes changing by a
diopter or less over the study follow-up.

A patient survey was administered to all study subjects at the one year
examination. Now, since several subjects mailed their surveys before the
one year examination, we are reporting on the total of 130 subjects. Not
all survey items were applicable to every subject. Thus, there is a
different total number of subjects for each survey item.

93.8 percent of bilaterally implanted subjects were able to perform most
daily activities without spectacles. This is in an average age of 69
years. We learned, too, that we had a fairly visual demanding cohort
with a large proportion of these subjects actively working on the
computer, driving, etc.

When specifically asked, \"How often do you wear spectacles,\" the
majority of our bilaterally implanted subjects responded, \"Almost none
of the time.\" Only 11 percent of subjects indicated any significant
spectacle use at all.

Overall quality of vision was rated as very good to excellent by 82.5
percent of the bilaterally implanted subjects. In fact, only four
subjects reported poor near vision with none reporting poor intermediate
vision or poor overall vision. None of those four subjects had worse
vision than 20/40 at any distance.

Now, I would like to close this section of our presentation by
illustrating the functional vision that a patient can achieve by having
at least 20/40 uncorrected near vision. Some of our favorite literature,
indeed, is easier than 20/40 such as the blue journal at 20/50 8 point
font.

Looking at 20/40, therefore, or better visual acuity in our cohort, the
accommodative functionality of the CrystaLens was clearly established
with measurement of near and intermediate acuity through the distance
correction to eliminate the confounders of myopia and astigmatism.

Distance corrected near visual acuity of 20/40 or better was achieved by
90.1 percent of the primary eyes and 100 percent of the bilateral
subjects. To further illustrate the range of vision, intermediate visual
acuity distance corrected was achieved by 99.6 percent of the primary
eyes and 100 percent of all the bilateral subjects. That represents all
but a single primary eye.

More importantly, 89.6 percent of the primary eyes and 100 percent of
the bilaterally implanted subjects achieved both near and distance
visual acuity of 20/40 or better through their distance correction.
Again, this metric establishes the functionality for an accommodating
IOL by eliminating myopia and astigmatism.

Finally, for a patient\'s perspective we looked at our bilaterally
implanted subjects over the range of acuities measured without glasses
in a real life setting. Again, please keep in mind that the mean age of
this population was over 69 years.

Given that fact, 93.5 percent read 20/32 or better at near, 100 percent
had an uncorrected intermediate vision of 20/32 or better, and 97.6
percent achieved uncorrected distance acuity of 20/32 or better.

It\'s now my pleasure to introduce Dr. Michael Colvard.

DR. COLVARD: Thank you, Steve. Good morning. I\'m Mike Colvard and I
served as a study investigator and I have financial interest in C&C
Vision.

I\'ll be presenting the results of the substudy conducted by C&C Vision
to evaluate the performance of the CrystaLens under low light or mesopic
conditions. This substudy was undertaken to address concerns related to
the 4.5 millimeter optic by comparing contrast sensitivity in eyes
implanted with CrystaLens with a matched group of subjects implanted
with standard intraocular lens.

The subgroup of total CrystaLens population and a matched cohort of eyes
were implanted with the standard IOL constituting the study population.

Control group of implanted eyes with standard IOL met the same
eligibility criteria as the CrystaLens population and underwent surgery
during the same period of time. Contrast sensitivity was measured at
three to six months postoperatively or later and if posterior capsular
classification was present, the testing was delayed until after the YAG
capsulotomy had been performed.

Equipment used was the Stereo Optical Optic 1600 vision tester. Testing
was performed with mesopic lighting of 3 cd/m2. Patients were allowed to
dark adapt for 10 minutes after which the mesopic testing was performed
with and without a glare source of 3 lux. Units were calibrated for
measurement at 20 feet.

A ratio of two to one of CrystaLens versus standard IOL was selected.
The sample size of 125 CrystaLens implanted eyes and 64 control eyes was
determined. This provides an 80 percent power to establish the contrast
sensitivity for the CrystaLens group is not worse than the standard IOL
group with a significance of .05, an acceptable difference between the
two groups of .12 log units.

In this test patients were asked to review a series of eight patches at
each of five spatial frequencies ranging from 1.5 cycles per degree to
18 at decreasing levels of contrast. As shown on this slide, there were
no differences between the CrystaLens and the standard IOL groups at any
spatial frequency when testing was performed with mesopic luminance
without glare. The addition of a glare source showed no difference
between these two study groups.

In summary, there was no difference in contrast sensitivity between the
CrystaLens and the standard IOLs. Importantly, glare had no effect on
contrast sensitivity outcomes in the CrystaLens implanted eyes.

I would now like to present the safety results for the CrystaLens
clinical trial. Cumulative adverse events are those which occur at
anytime over the course of the study in contrast to persistent adverse
events which are present at the time of one year visit.

In this slide the cumulative adverse events were all primary eyes. You
can see that there was one case of endophthalmitis and one case of
hyphema both of which were reported from non-U.S. sites, two secondary
surgical interventions and 12 cases of CME. All these were diagnosed by
fluorescent angiography.

Two secondary surgical interventions consisted of a vitrectomy and a
lens repositioning. The incidence of CME higher in the study group than
the FDA grid 3.7 versus 3 percent.

Cumulative adverse events for all 497 implanted eyes are shown here.
There was one additional case of CME in one fellow eye and four
additional secondary surgical interventions. The secondary surgical
interventions consisted of one lens repositioning when a small tear was
noted postoperatively in the anterior capsule, two explanations, and a
paracentesis.

The paracentesis was performed to reduce intraocular pressure on the
first postoperative day. One explanation was the result of an incorrect
power selection. The other explanation resulted from an excessively
large capsulorhexis that allowed anterior vaulting of the lens.

As shown on this slide, of the 13 eyes diagnosed with CME, only five of
the eyes have visual acuity of 20/40 or worse at the time of diagnosis.
At the last available visit best corrected visual acuity was 20/40 or
better for all eyes with the exception of a single eye with posterior
capsular classification.

In summary, seven of the 13 eyes had best corrected visual acuity of
20/25 or better at the last available visit, 10 eyes of 20/32 or better
and all eyes with the exception of a single eye with posterior capsular
classification with 20/40 or better.

Persistent adverse events are events present at the one-year follow-up.
As shown on this slide, four persistent adverse events were reported of
three primary eyes implanted with a CrystaLens, one eye presented with
both CME and iritis at one year.

This eye had residual cortex in the anterior chamber at the end of
surgery that was still present at the one-year visit. The second eye had
persistent iritis at one year. A third eye in this group had persistent
CME at one year. Overall, the percentage of eyes with iritis and with
CME was slightly higher than the FDA grid values.

This slide shows persistent adverse events in all 450 implanted eyes.
You can see that there was one additional case of iritis and one
additional case of CME each reported in one patient.

Persistent adverse events for the total study population of 450
implanted eyes is shown here. Iritis and CME were reported together in
one eye of a single patient. At the last follow-up all eyes had best
corrected visual acuity of 20/32 or better.

In conclusion, the CrystaLens has a solid safety profile. The incidence
of iritis and CME are higher in the safety cohort of primary eyes than
the FDA grid of historical controls. However, at one year all the study
eyes with CME or iritis had best corrected visual acuity of 20/32 or
better. No serious or unanticipated adverse events related to the
CrystaLens were reported at anytime during the course of the study.

I would now like to introduce Dr. Adrian Glasser, University of Houston,
to discuss results of testing for accommodation with the CrystaLens.

DR. GLASSER: Thank you, Michael. Ladies and gentlemen of the panel and
the Food and Drug Administration, my name is Adrian Glasser. I am a
consultant for C&C Vision and I have a financial interest in the
company.

There has been a long-standing debate as to what the mechanism of
accommodation is, how it should be assessed, and the mechanism by which
it occurs. A quote that I often use from Helmholtz\'s Treatise on
Physiological Optics emphasizes the long-standing debate that continues
today.

Helmholtz wrote, \"There is no other portion of physiological optics
where one finds so many differing and contradictory ideas as concerns
accommodation of the eye. Where only recently in the most recent time
have we actually made observations where previously everything was left
to the play of hypotheses.\"

Almost 80 years later Michaels wrote, \"Accommodation is one of those
subjects about which much that is supposed to be known has yet to be
discovered. The anatomy is controversial, the mechanics theoretical, the
innovation doubtful, the stimulus debated, the resting state in flux,
the pharmacology uncertain,\" etc. Much of this uncertainty still exist
today.

This slide shows several authoritative definitions of accommodation. The
two dictionary definitions identify a causal role in accommodation from
changes in the crystalline lens surface curvatures.

These two statements were made about the physiological accommodation
with the natural crystalline lens in the eye. It has been difficult to
define accommodation and to ascertain the accommodative mechanism in the
phakic eye. It is equally difficult to define and characterize the
mechanism of pseudo phakic accommodation.

More clinically accepted, although no more or less accurate definitions
of accommodation, include that from Tscherning and Griffin. The C&C
Vision CrystaLens does not undergo a change in lens surface curvature.
So from a clinical perspective the working definition of accommodation
considers the range of clear vision that patients experience or the
dioptric distance between the near point and the far point.

The C&C Vision CrystaLens was designed to capitalize on forward movement
of the optic that was observed to occur with an accommodated effort in
pseudophakes with plate lenses.

As shown before, the proposed mechanism of action of the C&C Vision
CrystaLens is to move the optic forward in the eye with the contraction
of the ciliary muscle through an increase in vitreous cavity pressure.

In 1999 when this IDE was first presented to the FDA and the clinical
trial initiated, pseudophakic accommodation was a relatively new
concept. Although there is now considerably more interest in
pseudophakic accommodation, there are still no studies that have
validated clinical methods to measure pseudophakic accommodation.

While clinical refractometers work well in normal phakic eyes, the
testing is often difficult and inconsistent in pseudophakes. Just as
accommodative lens technology is in its infancy, so too is the
technology for reliable pseudophakic accommodation measurement.

Clinically postoperative refractive outcomes in cataract patients are
most often assist quite simply with best corrected distance acuity
behind the foropter.

Having said that, in the CrystaLens clinical trial 10 eyes of five
subjects underwent more extensive accommodation testing by one of the
clinical investigators. This testing was done using tests that the
investigator was familiar with and uses clinically to assess
accommodation.

There is no question that some of the methods used are not objective
tests. The tests included dynamic retinoscopy and defocus with minus
lenses. In addition, a Tracey wave tracing wavefront aberrometer was
used.

Accommodative movement of the IOL was also assessed with A-scan
optosenography. On one occasion when accommodation was first paralyzed
with 1 percent cyclopentolate and then again at a later time when
accommodation was stimulated with 6 percent pilocarpine.

The A-scan data show a consistent decrease in anterior chamber depth and
the forward movement of the CrystaLens. If an IOL moves forward in the
eye, this would cause an accommodative change in power with the eye,
i.e., pseudophakic accommodation.

Although the testing was done in only a limited number of eyes with both
subjective and objective tests, the study results show with one
exception consistent changes that are representative of accommodative
change.

The sponsor acknowledges Dr. Bradley\'s valid concerns about the
limitations of the accommodation testing performed. But the measured
change in anterior chamber depth shown here show a forward movement of
the CrystaLens in nine out of 10 eyes.

The sponsor agrees that these data by themselves do not prove the
mechanism of accommodation. Having said that, the lens was designed to
move forward with an accommodative effort and the limited data shown
here suggest that this is occurring.

This study determined the best distance corrected intermediate and near
visual acuity and the add power required to achieve the best possible
near vision. In the contrast sensitivity substudy already described,
CrystaLens subjects were compared to a group of subjects implanted with
a standard IOL.

As described earlier by Dr. Slade, all patients implanted bilaterally
and nearly all with an implant in only one eye achieved excellent near
vision through the distant correction with 90 percent of the primary
eyes and 100 percent of the bilaterally implanted subjects achieving
20/40 or better. Again, this shows the near visual acuity measured with
the confounding factors of myopia and astigmatism removed.

Excellent results were found for the intermediate visual acuity measured
through the distance correction as presented earlier by Dr. Slade. All
but a single primary eye achieved intermediate visual acuity through the
distance correction of 20/32 or better at one year.

The add required to achieve best near visual acuity was evaluated in the
CrystaLens and standard IOL subjects in the substudy. Where the
CrystaLens subject had a mean measured add of 1.24 diopters, the
standard IOL group required a mean measured add of 2.36 diopters.

The graph shows a clear distinction between the CrystaLens subjects and
the standard IOL subjects with regard to the add required to achieve
best near acuity. The data suggest that the CrystaLens is providing far
better functional near vision than the standard IOL and asserts to
establish the functional accommodation provided by the CrystaLens.

Here the distance corrected near visual acuity of the CrystaLens
subjects were compared to those of the standard IOL subjects. While 35.9
percent of the standard IOL subjects achieved distance corrected near
visual acuities of 20/40 or better, 89.3 percent of the CrystaLens
subjects achieved this.

Testing was performed during the same postoperative period and the same
inclusion criteria were used for the two groups. The testing conditions
were identical for the two groups. The difference between the two groups
is the IOL. The CrystaLens was designed to capitalize on the observed
tendency of plate lenses to undergo a forward movement with an
accommodative effort.

Clinical testing shows that significantly more CrystaLens patients have
functional distance corrected intermediate and near visual acuities than
patients with standard IOLs. It may be unclear how much of the benefit
of the CrystaLens is due to active dynamic accommodation, depth of
focus, or ocular aberrations. However, what is clear is that the
CrystaLens appears to perform in accordance with the principles for
which it was designed.

In summary, despite years of study the mechanism of physiological
accommodation is still not fully understood. Pseudophakic accommodation
is a new concept and its mechanism is also not fully understood.

The objective measurements of changes in anterior chamber depth show
forward movement of the CrystaLens. The near and intermediate visual
acuities measured through the distance correction provide evidence of
accommodation consistent with the proposed mechanism and the objective
measurement.

This is further established by the fact that the CrystaLens subject
required 1.12 diopters less add to achieve best corrected near acuity
than subjects implanted with a standard intraocular lens.

Dr. Slade will now summarize and conclude our presentation.

DR. SLADE: Thank you, Adrian. In summary, accommodative functionality of
the CrystaLens was clearly established in this clinical trial with
measurement of near and intermediate visual acuity through the distance
correction to eliminate the confounders of myopia and astigmatism.

Distance corrected, near visual acuity of 20/40 or better was achieved
by 90.1 percent of the primary eyes and 100 percent of the bilaterally
implanted subjects. Intermediate acuity through the distance correction
of 20/40 or better was achieved all but a single primary eye.

Further, 89.6 percent of the primary eyes and 100 percent of the
bilaterally implanted subjects achieved both near and distance visual
acuity of 20/40 or better through their distance correction. 93.5
percent read 20/30 or better at near. 100 percent had an uncorrected
intermediate vision of 20/32 or better. And 97.6 percent had an
uncorrected distance acuity of 20/32 or better.

To conclude, the CrystaLens was designed to provide patients with a full
range of clear vision without glasses from near through intermediate and
far vision. The results of this PMA clinical trial demonstrate that this
goal has been exceeded with over 98 percent of the bilaterally implanted
subjects achieving the full range of near, intermediate, and distance
vision without glasses.

Thank you very much for your attention and this concludes the sponsor\'s
presentation. Thank you.

CHAIRPERSON WEISS: Thank you, Dr. Slade. I would ask the sponsor if they
could all take seats at the table, we\'ll be going into the 30-minute
question period from the panel.

I have one question in terms of the definition that you gave by Griffin
for accommodation, the ability of the eye to afford clear imagery of a
stimulus object over a range of distances. Wouldn\'t a multifocal eye
well then be classified as an accommodative eye well through that
definition?

DR. GLASSER: This is Adrian Glasser. Technically, yes, with one
distinction. The multifocal IOL achieves that result through a very
different cause than a monofocal IOL. The CrystaLens is not designed to
have multifocality to it so the required action of the lens is the
reason that the near, intermediate, and distance visual acuity is being
achieved.

But certainly multifocal intraocular lenses were designed for that very
reason, to provide functional near and distance vision. One additional
feature that an accommodative intraocular lens would provide would be
the full range of clear vision, not just near and distance vision that a
multifocal lens may provide.

CHAIRPERSON WEISS: Just a second question and then we\'ll go on to Dr.
Matoba.

You have both near and distance visual acuity for eyes that were in the
plus and minus half diopter of Plano. I noted that you did not have that
for intermediate visual acuity. Was that done for intermediate visual
acuity as well?

DR. BREEN: I\'m Michael Breen. I\'ll repeat my name again. My name is
Michael Breen. Those were unilateral uncorrected visual acuities. We did
not take or did not measure unilateral uncorrected visual acuity for
intermediate vision. That\'s why it wasn\'t presented.

CHAIRPERSON WEISS: Thank you.

Dr. Matoba.

DR. MATOBA: This is Alice Matoba. In the protocol I did not see a
detailed description of how the manifest refraction was carried out. I
wondered if you had given a certain standard protocol for the MR because
there is a subjective component both for the patient and for the
refractor.

If you slightly under-correct a myop, then you\'ll have uncorrected
visual acuity at a distance of 24 or better and better near vision as
well. Was it mast or was there some standardization for the manifest
refractions?

DR. BREEN: This is Michael Breen. I think great pains were taken to make
sure that standard procedures were followed with the manifest
refraction. The one thing that we did at the three exam which is at one
month was to perform a cycloplegic exam which really gave a definitive
idea of what the patient\'s refraction was.

There was a specific refractive procedure followed for every refraction
to take great pains not to over-minus the patient but also not to
over-plus the patient so that we wouldn\'t get inaccurate visual acuity
measurements when we were measuring the distance corrected intermediate
vision and the distance corrected near visual acuity.

DR. MATOBA: Were the refractions masted?

DR. BREEN: No. The refractions were not masted.

CHAIRPERSON WEISS: Dr. Grimmett.

DR. GRIMMETT: Hi. Michael Grimmett. I have a couple of questions, couple
of housekeeping ones. The first one in the criteria it list don\'t
implant the lens if the capsule or axis size is too large. Indeed, one
lens was explanted for that reason.

I assume that was judged or measured intraoperatively. Was there a
methodology? How exactly did the surgeon know just as a matter of course
when he tears a capsule or axis, how large did he know it was?

DR. SLADE: Stephen Slade. We aim to have a capsulotomy around 5
millimeters. The surgeons use different ways to judge that, either a
metric or a rule or calipers. But the one patient that did have an
explant actually was an oval capsulotomy and the lens was implanted
along the long axis of that capsulotomy and did bulk forward. That did
not occur except in that one oval capsulotomy case.

DR. GRIMMETT: So they were using some calibers over the cornea to have
an estimate.

DR. SLADE: Right. Different surgeons use different techniques.

DR. GRIMMETT: All right. The second question. In Vol. 2 of your manual,
I think in Appendix 2, was I think all the protocol forms that you used
and all the questions that were answered collecting the data during the
study.

There was one particular question that I would be interested in the
answer if it exist. Maybe I just didn\'t spot it in the materials. Page
264 of Vol. 2 had a question at the top that list, \"Most people
experience some visual disturbances such as glare or halos from looking
at oncoming headlights and driving at night.\"

Since your surgery have these disturbances (a) increased, (b) decreased,
or (c) not changed? While I did find tables for night driving activity
like Table 10.7, I didn\'t really exactly see that question answered. Do
you have the data for that?

DR. GORDON: I\'m going to have to look it up.

DR. GRIMMETT: Okay. I would appreciate it. Thank you.

My third question. In Vol. 1 \-- sorry about the tabs here \-- Vol. 1,
Tab 13 under the summary, page 184. I\'ll let you turn to that. Do you
have it? Okay.

At the bottom where there is a figure 13.2 that list the rate of visual
disturbances, specifically glare, halos, and nighttime driving vision
for the CrystaLens shown in the white boxes versus a standard IOL which
was pulled out of a study by Rogers, Steiner in Ophthalmology in 1999.

It was rather counterintuitive to me that a lens with a smaller optic
would have a lower rate of glare, halos, and night driving vision
difficulty than a lens with a larger optic. I\'m sorry I didn\'t pull
Rogers, Steiner\'s study but what was the standard IOL that he was
using? Do you know was that an AMO standard lens?

DR. SLADE: Steve Slade. I think I can partially address that. I believe
that was Rogers AMO study with a 6 millimeter optic. Of course, when you
are comparing two surveys from two disparate studies, we found it
significant really that we weren\'t worse and grateful that we were
better.

A lot of that has to do with centration because of the length of the
haptic lens from a surgeon\'s viewpoint centers beautifully. It also has
nothing intruding within the optic. A staked haptic IOL does have the
optics intruding within that 5.5 or 5.6 millimeter optic where this has
nothing.

Primarily I believe it was due just to the centration. It centers better
than any lens that I\'ve had experience with.

DR. GRIMMETT: And then my final question at this time. There was some
issues raised regarding the fatigue factor, the hinge, with one million
cycles being tested. I just want a clarification. All these calculations
about one million cycle failure.

Your test did not show that it failed at one million. In fact, it showed
that there was no visual fatigue at one million and the actual fatigue
time is unknown. It\'s greater than a million somewhere. Correct?

DR. SLADE: We got tired of watching it flex. That is true.

DR. GRIMMETT: So all these calculations that are basing off one million,
that was a time point that it did not show fatigue.

DR. SLADE: We did not see any failures. No, sir.

DR. GRIMMETT: Thank you.

CHAIRPERSON WEISS: Dr. Young.

DR. YOUNG: I\'m Dr. Young. It\'s interesting that the subjects who
underwent YAG posterior capsulotomy retained good, near, and
intermediate visual acuity and presented a common functionality.

One would expect that this functionality might be compromised once the
posterior capsule is disrupted as it can no longer transmit increased
posterior vitreous pressure forces forward to effect an IOL shift
anterially. This is especially interesting in this older aged population
with increased likelihood of vitreous syneresis and liquefaction.

I did note that in your presentation that you now are recommending a
limitation of the capsulotomy size to 4 millimeters or less. The
mechanism still as a puzzle may provide some variability with YAG
capsulotomy. Can you comment on that?

DR. SLADE: Right. Steven Slade. I\'ll be glad to comment about that. the
patients that had YAG capsulotomy did not show a decrease in their
functionality. The CrystaLens is not a bag issue. It does fixate in the
bag. The atropine allows it a chance for the specific little polyamide
loops to be fibrosed down and captured. But it is really increased
pressure, not the vitreous.

These patients obviously had posterior vitreous detachments in a lot of
cases. It\'s not that. It\'s the vitreous cavity, pressure within the
vitreous cavity which really would not make a difference then whether
there is a capsule or just the lens itself. It\'s pushing against the
lens whether it\'s had a YAG or not.

The capsulotomy on the YAG was kept, we recommend, at 4 millimeters or
less because we don\'t want vitreous coming around. Just one additional
point, back to the glare with Dr. Grimmett\'s comments. This lens is
posteriorly positioned dramatically more, as you saw in the photograph,
than a standard IOL.

If you figure out on a schematic eye the farther back you push it, the
larger the image would be projected then upon the cornea so it actually
functions at a larger \-- we calculated 5.4 \-- than typical. That also
might speak to the relatively low incidence of glare. Did that answer
your question?

DR. YOUNG: Yes. In your second limited study of 10 patients, did any of
those patients undergo a YAG capsulotomy?

DR. SLADE: That was a subset from another investigator that was not
myself but Dr. Dell. I don\'t know if any of Dell\'s 10 subset underwent
a YAG.

DR. BREEN: I\'m Michael Breen. Yeah, we would have to look that up to
make sure on that.

CHAIRPERSON WEISS: Dr. McMahon.

DR. McMAHON: Tim McMahon. Continuing along the same lines as Dr. Young,
in your draft labeling you discuss the posterior capsular disruption
that is indicated not to implant the lens.

Is that what you intend or is it that there will be a limitation in your
near visual acuity potential from that? I want some clarification that
if you have a tear in the capsule and a need, for example, for an
anterior vitrectory, are you going to advise surgeons not to implant
this lens?

DR. SLADE: Stephen Slade. I can address that. We do mean that. If there
is a tear in the posterior capsulotomy and an anterior vitrectory, we
would suggest that it is not implanted. This lens to function requires
to be within the capsular bag. It\'s a bag lens.

It also being longer is tensioning the capsular bag. In any patient
personally with any sort of capsular tear of vitrectory I wouldn\'t use
a capsular in anything that would fit into the capsule. I would go to
the sulcus. Since this lens is not designed to put in the sulcus, I
think the surgeon should go to a different lens.

DR. McMAHON: Thank you. The second you mentioned that is a biconvex
optic. Is it a bispheric optic?

DR. BREEN: Michael Breen again. It is biconvex and bispheric, yes.

DR. McMAHON: Thank you.

CHAIRPERSON WEISS: I\'m sorry. Do you have another one?

DR. McMAHON: One more. That is, you indicate in your surgical protocol
to use for atropine on two occasions, post-op and immediately post-op.
Is there specific justification for that? Is there evidence of that as a
requirement?

DR. SLADE: The theory \-- Stephen Slade again. The theory with the
CrystaLens was to atropinize the eye to give the polyamide haptics a
chance to be sealed down as a capsular bag seals down. We wanted to put
the eye at rest during that.

We initially started out with a week to two weeks of atropine and have
cut it back to once at the time of surgery. The recommendation would be
once at the time of surgery and then on the first day.

DR. McMAHON: I understand the principle. I was asking if you actually
have any data or evidence to suggest that it makes any difference at
all.

DR. SLADE: Have we implanted \-- okay. To that we would have to implant
CrystaLens without atropine. I don\'t believe that was done.

DR. GORDON: Judy Gordon. This was not assessed in a controlled fashion
but there was early experience outside of the U.S. suggesting that the
atropine did provide some benefit and allowed the lens to position in
posterior fashion without an early movement.

DR. McMAHON: Thank you.

DR. SLADE: I\'ll just add one more comment. In sites outside the U.S.
where it was not followed \-- the atropine protocol was not followed,
the results were not as good. Interestingly not our own studies but
other investigator studies of plate haptic IOLs with atropine in
mimicking this protocol did not achieve an accommodative effect. It does
have to do with the specific lens and the atropine does seem to make a
difference.

CHAIRPERSON WEISS: Mr. McCarley.

MR. McCARLEY: I just have two quick questions. Can you describe the
control population a little bit better whether or not these were similar
type lenses or whether these were completely different type design
lenses? No. 2, did you see any differences in the amplitude of the
accommodation in the power ranges that you were using in this study?

DR. BREEN: This is Michael Breen. In relation to the standard IOLs that
were used in the substudy there was a variety of IOLs and a variety of
material so it wasn\'t one specific lens. All of the lenses were 6
millimeter optic sizes with the exception of four that were 5.5
millimeters.

MR. McCARLEY: So they weren\'t plate haptic type lenses? They were
standard 6 millimeter and so forth?

DR. BREEN: Yeah. There were no plate haptic lens in that substudy group.

MR. McCARLEY: The second question was whether or not there was any
difference in the amount of accommodation you saw in different ranges of
powers.

DR. SLADE: Stephen Slade again. We did look at that and there was not.
Whether that is a combination of the different powers, the higher power
lenses being in a different length of an eye and that equalizing out, it
did not seem to make a difference. One update in the 10 patient
substudy. You asked the question about YAG. There were no YAG
capsulotomies in that group from Dr. Dill.

CHAIRPERSON WEISS: Dr. Ho.

DR. HO: Congratulations on some concise presentations this morning.
Intervention bias is always dangerous either from the subject receiving
a procedure or a drug, or from the standpoint of an evaluator of an
outcome. Can you just clarify in my mind to what extent masking was
used?

DR. BREEN: This is Michael Breen. This was not a mast study.

DR. HO: Okay. Specifically I was thinking about the contrast sensitivity
measurement. All patients that in your comparison groups, for example,
with CrystaLens versus heterogenous group of posterior chamber lens
implants knew that they were in separate groups at the time.

DR. BREEN: That\'s correct.

DR. HO: Okay. One of the exclusion criteria, going back to inclusion,
exclusion was age-related macular degeneration. What was the definition
of that for clinicians that were normal patients?

DR. GORDON: Judy Gordon. There were no specific criteria. It was really
a clinical judgment but there was a requirement for best potential
acuity of 20/32.

DR. HO: And that was established by?

DR. GORDON: I think a potential acuity meter. Also just to note as an
added note, typically in clinical trials of intraocular lenses there
would be an analysis of best case cohort versus worse case assuming that
postoperatively you would note additional cases.

But I think in screening the patients for best potential acuity, there
were a very small number of worse case patients and, for that reason, we
analyzed the entire cohort. I think there were under 15 cases
postoperatively so we decided to include every one.

DR. HO: I appreciate that, and the fact that there was no difference
between best and worst.

Another question I have with respect to potential retinal
contraindications for this. I would agree that in most of these senior
patients the vitreous \-- you don\'t want to think of this as a vitreous
face movement because it is essentially water in the operating room. I
could believe a hypothesis of just pressure.

One of the exclusion criteria was progressive ocular degeneration. I
think about high myopes for an excessively large eye. Were they
excluded, per se, and, if so, what were the parameters?

DR. SLADE: Stephen Slade again. They weren\'t excluded per se but the
lens power range that we had, we had a limited range of manufactured
power so, indeed, we didn\'t do high myopes or high probes on either
side because the powers weren\'t manufactured.

DR. HO: Thank you.

CHAIRPERSON WEISS: Dr. Bradley.

DR. BRADLEY: The sponsor finished with a very simple statement and
simple conclusion. In the summary they stated that the CrystaLens was
designed to provide patients with the full range of clear vision without
glasses. I emphasize the notion of clear vision. The conclusion made by
the sponsor was that the lens has succeeded in doing this.

But it is clear from the acuity data that although these patients
generally are 20/20 with their best corrected distance correction while
looking at the distant target, I think it approaches 100 percent of them
\-- in order to get 100 percent meeting a criteria, we have to drop it
to 20/40 at near.

It\'s pretty clear that if they are 20/20 at distance and 20/40 at near,
they don\'t have clear vision. I just wondered if I am interpreting that
correctly. The sponsor thinks that they have shown that the lens
provides a full range of clear vision even though the acuity drops at
near. Just a clarification on that.

DR. GLASSER: Adrian Glasser. That is certainly an accurate assessment of
the results. The CrystaLens is designed to provide a certain amplitude
of accommodation. The claim is not that it is producing 5 or 6 diopters
that a young human eye might be capable of. Perhaps were a lens to
achieve that, then one could assess the near acuity to a level of 20/20.

In this case the claim is that the lens is producing perhaps a diopter
or so more than a standard IOL. On that basis I think it\'s a reasonable
realistic claim that the functional vision is provided to some degree at
distance intermediate and near.

DR. BRADLEY: I think that\'s right. I think that it is very important
because of the uncertainty about language here. We have had the sponsor
describe to us many definitions of what accommodation is and it is
pretty clear that even within the expert scientific community there are
certain disagreements about what accommodation is. The language that we
use here today and the product should include be very clear. When making
a summary statement that the product has provided a full range of clear
vision, I think this is a bit misleading because most people would
interpret that as clear meaning focused.

It\'s pretty clear from the data that it does not provide a full range
of focus or clear vision. I think just to remind everybody that we need
to be very clear \-- very clear and focused on this issue.

CHAIRPERSON WEISS: I think that is something that the panel can address
in labeling from the erudite patients that you must have in your
practice who are reading the Blue Journal at a 98 percent rate \--

DR. SLADE: Our waiting room is full of it.

CHAIRPERSON WEISS: \-- I notice that things then drop down to 77 percent
patients saying they could do most things. Then 57 percent of patients
saying they could read the newspaper and 38 percent of patients saying
they could do needlework. I guess it depends if you have an erudite
practice or a sort of stay-at-home-mom practice.

DR. SLADE: Yeah.

DR. GORDON: This is Judy Gordon. Perhaps I could add a response to Dr.
Bradley\'s very valid comments that the indication for use is specific
to providing near, intermediate, and distance vision. I think some of
the language used here is to provide a sense of what we think the lens
is doing, that the indication is quite clear as well in what the patient
might expect.

DR. SLADE: Stephen Slade again. Just one thing. What is a definition of
clear vision? The majority of the patients choose not to use their
spectacles so, to me, they are choosing then this vision with just this
lens rather than any augmentation so it\'s clear enough.

The other thing is that compared to what as no other aphakic solution
currently affords anywhere close to this amount of range of vision. I
think that is a large improvement.

Just one last comment. It is important to differentiate this from a
multifocal IOL. Multifocal IOL theoretically would provide peaks of
vision but not more of a functional vision.

A multifocal IOL I would disagree with it being able to be called
accommodating because a multifocal IOL presenting multiple images to the
retina whereas this is simply presenting one image at a time or one
focus at a time. Thank you.

CHAIRPERSON WEISS: Dr. Coleman, do you have any questions? Otherwise,
I\'m going to go around for a second go-around.

Dr. Matoba.

DR. MATOBA: Well, one side. I don\'t think that erudite and stay-at-home
moms are virtually exclusive.

CHAIRPERSON WEISS: I stand corrected.

DR. MATOBA: Okay. Now, moving on my question is my concern about the 4.5
millimeter optic. You had did the contrast testing and you have a
patient satisfaction surveys saying that they do not have more glare.

These were older patients, all over than 50, and they tend to have
smaller pupils. Do you have any data where you have stratified this
information by pupil size because they did see the range was up to 7
millimeters in your contrast sensitivities.

DR. GORDON: The analysis was \-- Judy Gordon \-- performed to assess the
effect of pupil size and there was no effect on the contrast sensitivity
outcomes by pupil size.

DR. MATOBA: And patient satisfaction in terms of a glare or seeing a
lens edge or things like that?

DR. GORDON: Those data were not stratified by pupil size. I think we
felt that in conducting fairly well controlled contrast sensitivity
study with a glare source was a more definitive way to assess the
effects. For that reason we chose control lens as patients implanted
with control lenses with larger optics.

CHAIRPERSON WEISS: Dr. Ho.

DR. HO: Based on this confusion of the definition of accommodation and
the mechanism, my suggestion and what I anticipate will be some
round-and-round discussions later which could save some time would be an
agreement to eliminate the word accommodating from the description and
it might actually simplify the issue and allow us to focus on what is
clinically meaningful for the patient; that is, visual function.

CHAIRPERSON WEISS: I think that\'s going to be a determination made by
the panel on the basis of the data in terms of the panel discussion and
labeling whether, indeed, the panel feels that this does prove
accommodation or not.

If there are no other questions, I just have \--

DR. YOUNG: I guess I would perseverate on sort of the physical mechanics
of this IOL. In an effort to aid the cataract surgeons using your
implant in the field, could you provide some rationale for why 12 weeks
post-op is the first time a YAG capsulotomy should be performed
especially since there is no issue with the YAG \-- I\'m sorry, the
posterior capsule being intact?

DR. SLADE: Stephen Slade again. The 12 weeks is what is standard for
plate lens. This lens will fixate much better and is much more stable
than a plate lens but that is simply from a plate lens guidance. In the
field it might turn out that you don\'t have to wait that long.

DR. YOUNG: I see. Okay. Would you recommend perhaps that this be a
comment that the effects of performing a YAG capsulotomy prior to 12
weeks are unknown for this particular lens?

DR. SLADE: Yes. We don\'t know the effects of doing that so that is
correct.

CHAIRPERSON WEISS: I have one final question and then we will take a
15-minute coffee break. You have a chart of 78 percent of primary eyes
had 20/40 or better uncorrected distance and near and this increased
about 18 percent and 96 percent with bilateral subjects.

How do you account for the discrepancy of the marked improvement of the
visual acuity uncorrected when they had bilateral? Would that be that if
you had a unilateral lens placed in the second eye and the surgeon got a
capsular tear, would that patient be impaired because they couldn\'t get
the lens placed in the second eye? I think it\'s page 17 of the
presentation.

DR. GORDON: This is Judy Gordon. Although this is better answered by a
clinician, I will comment that in all of these analyses and having been
involved in many studies of vision correction, bilateral outcomes are
generally substantially better than unilateral.

However, I think the consensus and the data that we have generated here
suggest that even in patients in whom only a unilateral implant may be
allowed if they have previously had another type of lens, or if a fellow
eye that is later operated on is not \-- you know, can\'t be considered
for this lens, the outcomes are still good for unilateral implants. We
are simply showing that it is improved with bilateral implantation.

CHAIRPERSON WEISS: Dr. Grimmett and then Dr. McMahon.

DR. GRIMMETT: Mike Grimmett. In follow-up to a comment by Dr. Slade
earlier, he was commenting that the CrystaLens situates posteriorly
approximately 8 millimeters back from the corneal plane which gives it
an effective IOL optical zone of 5.4 millimeters at the pupillary plane.

I want to know about that 8 millimeters posteriorly. Did that differ in
myopic versus hyperopic eyes and just intuitively thinking that a
hyperopic eye everything would be closer together and would they then,
therefore, have an effective optical zone at the pupillary plane. Is
that true or false and did the lens situate differently in hyperopes
versus myopes.

DR. SLADE: All of the calculations, theoretical calculations, as to the
actual position and as to the optical zone, we did not see a difference
when we looked at myopes versus hyperopes, lens powers versus lens
powers, but theoretically, yes. The father back it was situated, the
larger the effective optical zone that would be projected on the cornea.

DR. GRIMMETT: Mike Grimmett again. Then it would logically follow that a
high hyperope with less distance from the lens to the anterior corneal
surface would then possibly have a higher risk of glare with dim
illumination mydriasis, and things like that?

DR. SLADE: Well, we didn\'t see that. That might be balanced by that
being a more powerful lens, the high hyperope pupil in general than
myopes but we did not see that.

DR. GRIMMETT: Thank you.

DR. GLASSER: May I just make a correction? Adrian Glasser. The number
that you just mentioned, 8 millimeters posterior, that is not correct as
far as I\'m aware. The actual placement of the lens should be
approximately 5 and half to 6 millimeters posterior of the cornea. Eight
sounds a little \--

DR. GRIMMETT: I\'m referencing page 160 of 195 under Tab 11, contrast
sensitivity in Vol. 1. I\'ll let you turn to that page. On page 160 at
the bottom, four lines from the bottom, it says the IOL position is 7.95
millimeters from the anterior granial surface.

DR. GLASSER: Adrian Glasser again. I think that number was taken from
Stewart Cumming\'s published paper with plate lenses, not necessarily
data from the C&C Vision CrystaLens.

DR. GORDON: We have just confirmed \-- Judy Gordon \-- that is published
data. That was provided as background in this section of the PMA was not
data generated specifically on this lens.

DR. GRIMMETT: So then if the lens does situate closer than that figure,
those calculations on pupillary diameter to over estimate the optic size
would also change, that is correct. The 5.4 figure \-- the 5.4
millimeter effective optical zone at the pupillary plane is also
incorrect, that this lens sits closer to the cornea.

DR. GORDON: I think those measures are based on calculations but not in
vivo data generated from patients with the CrystaLens. I think this
reference that you are describing says 7.95 millimeters is published
data on plate lenses.

DR. GRIMMETT: Okay. And then in the studies where you did do ultrasound
or whatever mechanism you determined, where does the CrystaLens sit in
the very few patients that you have? If it\'s not 8 in the couple that
you, what is it?

DR. BREEN: Michael Breen again. In those patients the anterior chamber
depth measurements ranged anywhere from 5 millimeters to 6 millimeters.
Now, those measurements refer to the distance from the back of the
corneal surface to the anterior surface of the lens. These calculations
that were cited from Dr. Cumming\'s literature took into account changes
in vitreous chamber depth which refers more to the posterior surface of
the lens.

CHAIRPERSON WEISS: Dr. McMahon.

DR. McMAHON: Getting back to your question, Dr. Weiss, in addressing the
binocular vision. In addition to the concept of binocular summation, I
would suspect actually that the fact that the first eye of the binocular
patients the surgical instructions were to target to minus a half, and
the second eye to use the results of the first eye to aim for plano.

Under those circumstances that alone potentially can account for that
improvement in uncorrected vision. Does the sponsor agree?

DR. SLADE: Yes, we would agree with that.

CHAIRPERSON WEISS: Just another follow-up on that question and then we
will break. When you think there might be any issues if the patient had
a standard PCI well in a fellow eye and the CrystaLens in one eye, what
would they be using for their near vision? Would they just be using
monocularly with the CrystaLens? Would they be using specs? What do you
anticipate?

DR. SLADE: Stephen Slade. I\'ll take a stab at that. Theoretically, I
think it would depend on which lens was placed in the dominant eye and
which was placed in the non-dominant eye. I think it would also depend
upon what the refraction on it was.

I believe they would be using the CrystaLens \-- we have no data for
that. I believe they would be using the CrystaLens for the range, but I
think it would largely depend upon their resting refraction and which
was the dominant and non-dominant of each lens.

CHAIRPERSON WEISS: In your data it was mentioned that about 4,000 cases
have been done outside the United States. I have a page but I don\'t
want to waste anyone\'s time. For the cases that have been done outside
of the U.S., do they have any information as far as unilateral on the
implantation with PC IOL on the other one?

DR. GORDON: Judy Gordon. I don\'t believe that number has been implanted
outside the U.S. but I would have to look it up. We haven\'t collected
that information specifically.

CHAIRPERSON WEISS: Fine. I think we are all set with the question period
and we are going to break for 15 minutes. Let\'s all meet back here
promptly to begin the FDA presentation at that point.

Judy, I\'m sorry. Hold on one second.

DR. GORDON: Thank you for calling me. I just wanted to respond to Dr.
Grimmett. Unfortunately the survey case that you were looking at was an
older survey that was eliminated. It\'s in stay in the penal pack. If
you look at page 153 in Vol. 1, I think you will see the analysis that
you are looking for.

DR. GRIMMETT: You are referring to Table 10.7?

DR. GORDON: Tables 10.6 and 10.7. They are slightly different.

DR. GRIMMETT: Yeah, I saw there were different.

DR. GORDON: This particular question proved to be extraordinarily
confusing to us and to the patients and so a different question was
substituted.

DR. GRIMMETT: Too bad. I liked that other question.

DR. GORDON: Very hard to answer for a mean age of 70.

CHAIRPERSON WEISS: Actually, I\'ll just mention in terms of follow-up, I
think on page 7 in the blue book it says 4,000 units have been
distributed. I read that as implanted.

We now will break for 15 minutes.

(Whereupon, at 10:25 a.m. off the record until 10:40 a.m.

CHAIRPERSON WEISS: I\'m told the sponsor had a brief clarification they
wanted to make and then after Judy Gordon makes that clarification, we
will then start the FDA presentation.

DR. GORDON: Thank you very much. Judy Gordon. Just two answers \-- one
clarification and one answer. Two patients enrolled in the study did
undergo YAG capsulotomy before 12 weeks, between one and two months.
Those capsulotomies were performed safely and the patients had good
outcomes.

The second is a clarification for Dr. Ho. In fact, the contrast
sensitivity testing was performed by mast examiners at each site. The
patients were not masked because they knew if they had an
investigational lens or a standard lens. All of the examinations were
done in a masked fashion. Thank you.

CHAIRPERSON WEISS: Thank you. I\'m going to ask to begin the FDA
presentation.

Dr. Lepri, are you going to start, or Donna?

MS. LOCHNER: I just have a few brief introductory comments.

To introduce this PMA I would like to focus my comments on the
additional claims that C&C Vision proposes for their CrystaLens IOL
which the sponsor designates as an accommodating IOL.

For the purposes of this discussion, additional claims are the
extraordinary statements of clinical benefit that are contained within
the labeling, particularly in the indication section of the labeling.

As you know, most IOLs are indicated for primary implantation in the
capsular bag for the visual correction of aphakia following cataract
extraction. The C&C IOL also is indicated for patients who may benefit
from improved near, intermediate, and distance vision without
spectacles.

A central issue for your review of the extraordinary claims made by the
sponsor is whether you believe that the near and intermediate visual
acuity data and limited other objective outcomes as discussed earlier by
the sponsor adequately support the claim of accommodation.

We ask that you concentrate on the clinical and technical merits of the
claims and not necessarily on the exact wording to be placed in the
labeling. We are happy to receive any specific wording you may feel is
important but in any instance where you do not have strong preference,
we can work through wording issues at a later time.

At this time I would like to acknowledge the work of the FDA review
team. Don Calogero performed the team leading and engineering reviews.
Bernie Lepri and Gene Hillmantel did the clinical reviews.

Susanna Jones is the toxicology reviewer and Susan Gouge, microbiology.
Valerie Flournoy performed the Good Manufacturing Practices Review.
Sybil Wellstood from Bioresearch Monitoring. And Jack McCracken reviewed
the patient labeling. Now Dr. Lepri will present the FDA clinical
review.

DR. LEPRI: Good morning members of the panel, representatives of C&C
Vision, FDA members, and guests. I would like to begin by commending the
sponsor on a well-prepared document and their incomparable cooperation
with the FDA in preparing for this panel meeting.

I am then going to present to you FDA\'s questions regarding this
application but before I begin, I would like to give a special thanks to
Dr. Gene Hillmantel for his assistance to me in providing statistical
and clinical interpretations of the statistical analyses that he
performed on the accommodative substudies performed by the sponsor.

In preparation for addressing the first question, we would like the
panel to take into consideration some information that is very germane
to the fundamental objective of the indication of this device, the
achievement of near visual acuity through accommodation.

Outside of the requirements of protocol was conducted additional testing
in an effort to document the mechanism of action of the CrystaLens. That
is accommodation achieved by the forward and backward movement of the
lens optic along the axis of the eye.

This testing included dynamic retinoscopy, defocus, near point
evaluation, near vision through the distance Rx with cycloplegia, power
mapping with the Tracey wavefront aberrometer, and anterior chamber
depth analysis through A-scan. It is important to note that both
cyclopentolate and 6 percent pilocarpine were utilized in the studies.

The accommodative substudy summary data is presented in the following
chart. This table presents the summary of the accommodative substudies
and one can see that there is a wide spread in the dioptic results
measured ranging from 0.72 diopters to 3.14 diopters.

The .72 diopters was measured by the Tracey aberrometer and in dynamic
retinoscopy a very subjective technique that was measured to be an
average of 3.14 diopters.

Analysis of the correlation among these various forms of measurement of
accommodation reveals that the highest correlation among these findings
is between the Tracy aberrometer and the change in anterior chamber
depth as measured in diopters that correlation being 0.662. The lowest
correlation is a negative one, that being between dynamic retinoscopy
and aberrometry of minus 0.54.

Question No. 1. This is the first IOL that proposes accommodation as its
mechanism of action. (a) Do the effectiveness data support a claim of
accommodation? (b) What performance issues should be considered both
generally and for product labeling?

Information for question No. 2. The stability of the CrystaLens hinge
was demonstrated by in vitro dynamic fatigue testing up to one year and
analysis of change in the distance manifest refraction spherical
equipment between consecutive examination and (c) if by intermediate
visual acuity between consecutive examination.

The stability of the MRSE of primary eyes is presented in the following
table. One can see that on the average that 85 percent of the primary
eyes were within a half diopter and 96 percent were in the range of one
diopter, the distance manifest refraction spherical equivalent when the
measurements were made between form three to four and from form four to
form five.

The mean difference from the form three to form four interval was minus
0.03 with a standard deviation of 0.52. From form four to form five the
mean difference was 0.13 plus or minus 0.45. I believe that was for the
one diopter.

It then went on to analyze the stability of the uncorrected near visual
acuity. This table presents those results for the one year consistent
cohort. Approximately 81 percent for either form three to form four and
form four to form five were within one line of acuity as measured
between those consecutive intervals.

Approximately 13 percent of the form three to form four interval had an
increase of greater than or equal to two lines and at form four to form
five 14.5 percent had an increase greater than or equal two lines.

The intermediate visual acuity analyses through the distance correction
for the United States eyes is presented in the following table and is
stratified by primary eyes and fellow eyes. Approximately 80 percent of
primary and fellow eyes were 20/20 at intermediate test distances at one
year and 95 percent were at 20/25 or better by one year.

Question No. 2. Considering the previous data I presented to you, do you
believe that the sponsor has demonstrated the stability of the hinge
and, therefore, the stability of the accommodative refractive effect?

Question No. 3. Does the panel recommend any other modifications to the
proposed (a) physician labeling, and (b) patient labeling.

Question No. 4. Do the data in PMA P030002 support the proposed
indication statement as follows: Primary implantation for the visual
correction of aphakia in adult patients with cataracts provide improved
near, intermediate, and distance vision without spectacles. Thank you.

CHAIRPERSON WEISS: Thank you, Dr. Lepri.

We will now have a 10-minute session for questions to Dr. Lepri from the
panel. No questions?

Dr. Lepri, thank you very much for a very clear presentation.

We will proceed onto additional comments from the sponsor if they have
any.

DR. GORDON: Thank you. Judy Gordon, representing the sponsor. We have no
additional comments at this time. We will have some closing comments but
we would like to thank the panel and the FDA reviewers for working with
us from the beginning of this IDE to get to this review of this PMA.
Thank you very much.

CHAIRPERSON WEISS: Thank you.

In that case, we will then move things up a bit and go on to our panel
reviewers and begin with a presentation of the primary panel reviewer.
First we\'ll start with Dr. Arthur Bradley and then go on to Dr. Anne
Coleman.

EXECUTIVE SECRETARY THORNTON: Dr. Bradley, would you prefer if Dr.
Coleman went before you? Do you need some more time?

DR. BRADLEY: We were going to test this out over lunch but it might
work. If it works, we\'re ready to go.

CHAIRPERSON WEISS: Mr. McCarley has a question for Dr. Lepri so while we
are setting up, you can do that.

Dr. Lepri, Mr. McCarley has a question.

MR. McCARLEY: Rick McCarley. I had a question for Dr. Lepri. When I\'m
reading the indications for use, I just wanted to be clear because my
understand \-- I just want to be clear about my understanding of this.

It\'s for the primary implantation for the visual correction of aphakia
in adult patients with cataracts. Then the additional portion is provide
improved near, intermediate, and distance vision without spectacles.

Just for clarification, should the first portion be primary implantation
for the distance correction of aphakia which is a typical intraocular
lens indication? Then it would be to provide improved near and
intermediate vision?

DR. LEPRI: This is printed here in this slide as the sponsor had it
printed in their application.

MR. McCARLEY: I see.

DR. LEPRI: That\'s why we bring it to your attention now for
consideration for later.

MR. McCARLEY: Just a piece of clarification. Thanks.

CHAIRPERSON WEISS: Dr. Bradley, would you mind if we start with Dr.
Coleman perhaps while you\'re setting up?

DR. BRADLEY: Not at all.

CHAIRPERSON WEISS: Do you have any computer work?

DR. COLEMAN: No.

CHAIRPERSON WEISS: Fine. That sounds excellent.

DR. COLEMAN: I\'m very low tech.

CHAIRPERSON WEISS: The benefit of no computer these days. We are going
to start with Dr. Coleman as actually the revised schedule does show.

DR. COLEMAN: Thank you. I was going to basically summarize my review. In
terms of reading the question: This is the first accommodating IOL to be
reviewed by the panel.

Do the effectiveness data support a claim of accommodation? Are there
any issues related to the accommodative performance of the CrystaLens
that you believe should be considered either in general or for inclusion
in the device labeling?

Although there are different definitions of accommodation, I felt that
the effectiveness data did appear to support a claim of functional
accommodation for the CrystaLens since approximately 80 percent of
primary eyes had uncorrected distance acuity and uncorrected near acuity
of 20/40 or better.

In addition, because eyes within plus or minus half diopter of plano
were more likely to have a distance acuity and near acuity of 20/40 or
better, and because fellow eyes which were targeted for plano had a
greater frequency of uncorrected distance acuity and near acuity of
20/40 or better, I recommend changing the device labeling on page 2 for
aiming for plano instead of minus half sphere, although the
recommendation for the clinical trial was to aim for half sphere
correction.

In addition, the changes in the MSRE from postoperative months one to
two to months three to six, and for months three to six to months 11 to
15 are very relevant. Although approximately 96 percent of eyes had a
change of distance acuity of less than or equal to plus or minus one
diopter, I am concerned by the large range and the acuity difference
between the postoperative visits. Because a change of plus or minus one
diopter is felt to be relevant, I recommended presenting the data as the
percent that it changed as less than or equal to plus or minus 0.50
diopter or half diopter.

Including this information in the device labeling I felt would help
surgeons when evaluating this and also including the distance and near
acuity would also be helpful in evaluations by the surgeons. This
recommendation was done in the rebuttal.

The next question was to demonstrate the stability of the hinge design
of the CrystaLens. I\'m going over the in vitro dynamics fatigue test
and whether I believe that the sponsor had demonstrated the stability of
the hinge and, therefore, the stability of the accommodative refractive
effect.

I did some calculations assuming that the device fatigued at one million
cycles. At that it looked like you might only have 10 years of
accommodative ability or of flexibility of this device.

I felt that it was important to indicate in the labeling that this
device may have a limit in terms of it\'s flexibility and its ability to
give a range of different acuities without correction for individual
patients and the surgeon could evaluate that.

The uncorrected near acuity appeared relatively stable. Approximately 80
percent of eyes had a change in acuity with one line of acuity and
approximately 12 percent had an improvement in their acuity from
postoperative months one to two to three to six months. And then from
three to six to 11 to 15 months approximately 79 percent had a change in
acuity with one line, and approximately 16 percent had an improvement in
near acuity.

I did not find any data on the difference in intermediate visual acuity
between consecutive examinations. Then I also repeated my comments on
the MSRE related to question one.

In terms of providing recommendations for modifications or additions to
the labeling, recommendations that I had were that a warning precaution
that the effect of vitrectomy on accommodative performance of CrystaLens
is unknown. Include information from the patient\'s survey (Table 10.3)
in the labeling. This information is important for a surgeon\'s
discussion with potential patients regarding their expectations.

Mention range of axial length and lens powers that were used in the
study in labeling under precautions. Those axial length were 21.0 to
26.6 millimeters and lens powers of 16.25 to 27.5 diopters.

Mention that atrophy sulfate 1 percent should be given immediately
postoperating and postoperative day No. 1 on page 2 of labeling since
this is how the clinical trials were done.

Mention possible increased rate of CME associated with sulcus-bag
placement of haptics under adverse events.

Then in summary, I was asked, Do you believe that the data in the PA
provide reasonable assurance of safety and effectiveness? I felt that if
the above additions and modifications to the labeling are done in
addition to those that we recommend today, I believe that the data in
the PMA would provide reasonable assurance of safety and effectiveness.

CHAIRPERSON WEISS: Thank you, Dr. Coleman.

Dr. Bradley.

DR. BRADLEY: Sorry for the technical problem. I guess this will all be
done with when Bill Gates buys Mackintosh.

As some of you know, I have been working for the FDA for some time
reviewing all sorts of products that have no personal relevance to me.
Finally we have one that is going to provide people like myself with
accommodation in the aging second half of their life.

I am quite excited by such a product, let me tell you. I want to
formally announce to the public record and to the FDA that this is
absolutely the last PMA that I will review without a reading add.

So let\'s see if we can get through this. We all know the product. As
usual, I usually spend most of my time discussing the effectiveness of
the product. I really try to narrow it down to three questions.

Does it allow the eye to accommodate and by how much? What is or are its
mechanisms of action? This is certainly pertinent when it comes to
labeling. And does it provide adequate quality near vision? I think
those are the three keys issues we have to deal with regarding
effectiveness.

It\'s worth reiterating the really unique claim that this product has.
This IOL employs the eye\'s natural accommodated mechanisms to alter the
axial position of this IOL and in doing so alter the power of the eye.
We will call that accommodation.

Effectiveness concerns. Those of you who read my review are aware that I
have a few concerns. Let\'s go through them. Concern No. 1, does the
lens as claimed provide active accommodation and, if so, how much? This
is really the most interesting question of the day.

I looked through obviously a very lengthy document and tried to narrow
down the key points to one panel here. Let\'s list them as evidence for
accommodation.

Right at the top I put in my own bias. I like to see objective data
where possible. We have objective data. This was obtained with a new
type of autorefractor called Tracey on five subjects, 10 eyes. One eye
was seen like a clear outlier so I\'ve reduced it to nine eyes.

They observed the difference in refraction between an eye with
pilocarpine in it and the same eye at a different time with
cyclopentolate. The difference was on average slightly less than half a
diopter. This indicates that one can obtain a pharmacologically induced
accommodative amplitude of slightly less than half a diopter.

Second, the barometry is particularly important because it not only
tells us something about the change in the power of the eye but also the
mechanism. As you know, the proposed mechanism of this particular
product is that the eye well will move anterially and, in so doing, will
produce an increase in the overall power of the eye.

Again, 10 subjects \-- five subjects, 10 eyes. Again, data were taken
with the eye having cyclopentolate in it and with pilocarpine in it.
Under those two conditions the difference in the anterior chamber depth
was about .65 millimeters. We can conclude that we pharmacologically
induced accommodation. We have about a .65 millimeter movement of the
lens in anterior direction.

As Dr. Glasser pointed out to us, that is, in fact, the whole principle
behind this lens. This is data to support that, in fact, it does work as
designed.

How much accommodation should that produce? Well, it depends a little
bit on the actual positioning of the lens and the power of the lens, but
let\'s say about one diopter and would be indicated by that study.

Another really quite interesting study. In this case it was 126
subjects. I think it was made with the contrasensitivity substate. They
do what is called a near over refraction, and that is we want to find
out how much extra power do we have to add in order to get the near
acuity to maximum.

The evidence from that study indicates that about 1.1 diopter of
accommodative power provided by this IOL. How do I come to that result?
The difference between the near over refraction of the control group
which is a standard IOL and that of the CrystaLens group. The difference
between those two is about 1.1 diopter.

The difference between those two groups presumably is that the
CrystaLens group were accommodating. Therefore, the difference in the
over refraction power is an indication of the accommodative amplitude,
slightly over one diopter.

We have two datasets. Again, this is on the small substudy of five
patients. We\'ve 10 eyes each. Dynamic retinoscopy indicating over 3
diopters of accommodation. Clinical depth of focus study indicating
approximately 2.5 diopters of accommodation.

Both of these methods are notoriously difficult to do precisely. One has
to wonder how come when the three previous measures are indicating
between a half and one diopter these two measures are indicating between
2.5 and 3 diopters.

Next down the list. We end up now in the major part of the submission
which involved visual acuity measurements. By the way, these are
extremely difficult to interpret in terms of evidence for actual
accommodation. I have tried to summarize it in the following way.

First off, let\'s consider the intermediate visual acuity data through
the distance correction. In this case we\'ve got 368 samples. What was
the intermediate distance? It was 80 centimeters or 1.25 diopters.

It turns out through the CrystaLens the patients mean visual acuity at
intermediate distance was about 20/20. Although I couldn\'t find it, I
presume this is the same as the mean acuity of these patients at
distance through the distance correction.

That is, their intermediate acuity was basically the same as it was at
distance which is exactly what we would expect if the eye was
accommodating, or able to accommodate, 1.25 diopters. The evidence from
that visual acuity study is that it looks as though the lens is
providing 1.25 diopters of accommodation.

What about the near acuity? Much talked on. Near acuity was obtained at
40 centimeters. That\'s a 2.5 diopter at demand. The near visual acuity
through the distance correction, again 369 eyes, the mean acuity was
20/37. Clearly acuity has dropped when you went from the 80 centimeters
to the 40 centimeters.

Why has it dropped? There is one obvious reason. The image is now out of
focus. It is clear then from these data that the CrystaLens does not
provide 2.5 diopters of accommodation. There is no doubt about that.

My estimate from these data is that it is providing about one diopter of
accommodation. How do I come up with that number? Again, I am having to
speculate a little bit because, like I say, these data are very indirect
ways of estimating accommodation. The basic way I come up with this
number of one diopter is the following.

If we look at the control group that we studied with the standard IOL,
presumably these patients have no accommodating amplitude whatsoever. At
intermediate distance they had on average an acuity of 20/27. Presumably
at this intermediate distance they were 1.25 diopters defocus.

Under the test conditions of the study, it looks like 1.25 diopters of
defocus gives an acuity of 20/27. At near the patients with the
CrystaLens had an acuity of 20/37. The presumption is they are out of
focus by more than 1.25 diopters.

Let\'s say 1.5 diopters. So if they are out of focus by 1.5 diopters and
the target was 2.5 diopters, that means they could perhaps accommodate
by about one diopter. That\'s how I come up with that number.

So I put together the objective autorefractor data, the biometry data,
the near over refraction, the intermediate and distance acuities through
distance correction, and they all seem to point to between .5 and one
diopter of accommodative amplitude provided by the CrystaLens. When I
say accommodative amplitude, I mean that the eye is able to increase its
optical power by between a half and one diopter.

The unfortunate thing is that the two most compelling sets, the top two,
objective autorefractor and the biometry data were only carried out on
five subjects. Rather than obtain these data while the patients made an
accommodative effort, they were obtained by taking the difference in the
data between pilocarpine and cyclopentolate. It turns out that is far
from idea. In the end my provisional conclusion is indeed the CrystaLens
does seem to generate between half and one diopter of extra power and,
thus, we can conclude that it does show evidence of accommodation.

Let\'s move on to the next effectiveness concern No. 2. This is one of
mechanism. Like I say, this is quite important when we come to labeling.
Does the CrystaLens generate extra optical power in the eye by moving
forward as claimed while the patient looks at a near target? As I just
mentioned, the biometry data will keep for this mechanistic question.
The biometry data absolutely show that the lens did move forward.
Remember, it was only 10 eyes. The eyes were compared under these two
pharmacologically induced conditions. One with cyclopentolate and one
with pilocarpine.

So, as I said, this is far from ideal. Both drugs affect the action of
the ciliary muscle and that\'s the reason for using them in this case.
But it\'s very important to appreciate these drugs also affect the iris
muscles and that\'s these two anterior chamber measurement were made
with unnatural pupil sizes and may have been an influence by the extreme
dilation and contraction of the iris. My recommendation is the biometry
measurements should have been made while subjects viewed distance and
also near targets and the difference between those two measurements
taken. That would have been much more compelling. We would have had
evidence that, in fact, the CrystaLens does move forward during
attempted accommodation. At the moment we don\'t quite have those data.

Provisional conclusion. The CrystaLens can move axially as designed but
we have no evidence that it does so during near work which is
unfortunate.

Effectiveness concern No. 3. Does the lens provide sufficient near
vision quality to eliminate the need for a reading add. This is really,
I think, the strong suit of the sponsor coming in. They have collected
lots of data on visual acuity at near, at distance, intermediate. In
fact, most of their effort was placed on this sort of data collection.

They have used the visual acuity data at near in particular as evidence
that the lens is accommodating. They have encouraged us to accept these
visual acuity data as evidence of accommodation focusing our attention
on not necessarily the mechanistic activity of this lens but on the end
result.

Does it really work for the patient? I think that is a reasonable
approach. I have taken that approach here and come up with a concern.
See what you think.

In my previous analysis on amplitude of accommodation estimates, again I
came up with estimates ranging from half to one diopter from their data.
We can ask whether this is sufficient to provide functional vision
ethnia. How do we answer that question? There are lots of ways one
could. I had a look at the literature and came up with the following.

Typically patients request near adds during their early to mid-40s when
accommodative amplitudes are about one diopter. This analysis suggest
that the extra power provided by the CrystaLens may not be sufficient
and patients may still require a reading add.

How do I come up with that? The idea is very simple. If they have \-- if
the lens provides perhaps one diopter of accommodation and we find that
many people require a near add when they have one diopter of
accommodation, then one could suggest that maybe even though CrystaLens
will give about one diopter of accommodation, that may not be sufficient
to preclude the necessity for a reading add. That\'s the point there.

However, this is quite important because the IOL replacement is
occurring at a significantly older age than the 40 to 45-year-old age
group that I just talked about. The .5 to one diopter power change in
combination with senile pupil miosis may be adequate for near work.

That is, having one diopter of accommodation may be adequate as long as
your pupil is quite small as it will tend to \-- pupils tend to decrease
in size with age. In the end for this age group maybe one diopter is
adequate.

The sponsor did a patient survey and asked lots of questions. One that
particularly caught my eye, and I think Jayne Weiss mentioned it
earlier, is that when asked what proportion of these could read the
newspaper without spectacles it was about half, 57 percent.

One presumes that is you do not need a reading add, one could sit down
and read the newspaper without wearing such an add. It looks like 57 can
do this.

My provisional conclusion regarding this concern No. 3 is that the
CrystaLens may provide adequate near vision for about half of the
patients. By adequate I mean that they can sit down and read the
newspaper without a reading add.

It\'s worth coming back to a general concern that I think was
distributed throughout my review. That is that the study design to me
seemed rather odd. Here we have a product that has a very, very
plausible scientific basis.

That is, that there is a lot of evidence in theory and the way that the
product was designed and the way that the surgeons were trained to
install the lens all seem to indicate that this lens stood a very good
chance of providing old eyes with active accommodation. I mean, this is
a revolution to be quite honest. I mean, I was really excited by this
product.

Given all of the scientific background which leads us to think that this
lens surely will work, I was really disappointed that the sponsor did
not provide us with compelling data showing us the accommodative
responses of an eye with the IOL in place. I was really quite
disappointed about that.

Middle point there. The coupling of pupil size and accommodation is
accentuated when using cyclopentolate and pilocarpine. The impact of
pupil size on visual acuity is always magnified whenever the retinal
image is defocused. Because of the reliance on visual acuity and the
failure to control pupil size, much of the data is very difficult to
interpret.

We\'re not sure whether we\'re seeing the impact of pupil size change or
the impact of power change inside the eye. That\'s a very, very
difficult thing to separate because most influence visual acuity. I
think that is, again, in all study design.

It is clear that if you are going to validate a product like this, one
needs to assess changes in refraction using a controlled pupil size. Our
recommendation that the FDA in the future require more compelling
evidence of active accommodation, not near visual acuity, when
evaluating IOLs that claim to provide active accommodation.

I think this would help the panel in the future feel comfortable that
when a product claims to provide accommodation that, in fact, they have
demonstrated it really does. I think that becomes particularly important
when it comes to labeling.

In fact, I was making this slide when the schedule was accelerated so
I\'m not sure what it says myself now.

I think it is particularly important given the discussion this morning
and I think Dr. Glasser did an excellent job of summarizing some of the
ideas and uncertainties out there regarding even what accommodation is.
It seems unfathomable that we are still arguing about what accommodation
is but, anyway, we are.

I have done my own job here in another post hoc way. Hopefully Dr.
Glasser will not object. I sort of tried to press multiple definitions
into two types. Really there is one type which is accommodation is a
change in optical power in response to a change in object distance. When
you look at a distance target, you look at a near target, the eye
changes in power. It\'s a classic autofocus ability of the human eye. We
can either have that definition with or without the mechanism.

Definition No. 2. It\'s the dioptic range which visual quality meets
some criteria. We can have 20/40 from distance to near. That is another
type of criteria. The sponsor has preferred to use type 2 definition and
by employing a 20/40 criterion the optic range spans from distance to
near quite comfortably.

It\'s worth mentioning that although it\'s not true in this case, it is
important to appreciate that pinhole glasses \-- remember those? They
used to be marketed on airplanes. I think they must have assumed that
airline travelers are a bit stupid. Anyway, those pinhole glasses would
also meet such a standard. It is very important to realize, therefore,
thus showing what I would call the depth of focus of the eye at this
criterion, 20/40, 0 to 2.5 diopter, does not mean necessarily that the
eye has accommodation.

In this particular case, as I have said in that first slide, there is
plenty of evidence that the eye seems to be accommodating. It is very
important to appreciate that having this depth of focus with a criterion
like 20/40 does not necessarily mean there is accommodation.

Okay. Finally, to the questions posed by the FDA for the panel.
Effectiveness. Although it is unclear how the lens works, it clearly
provided superior near acuity compared to a standard IOL. In this
minimal sense, and by minimal I mean it is better than a lens that has
zero accommodation, it seems effective.

Let\'s continue that on. If we set the effectiveness bar a little
higher, we must assess whether the lens provides adequate near vision.
The analysis that I described and the sponsor\'s own survey data suggest
that it might in some but not in others. I will call that a marginally
effective product.

Issue No. 2, stability of the hinge. The hinge is clearly capable of
more than 1 million movements. Again, without in vivo data it is unclear
if it moves in the eye while viewing distance targets. We really don\'t
know what\'s going on in the eye. It\'s hard to interpret the 1 million
number but it looks to be a pretty stable product.

Labeling. Here, I think, it is very tricky because of this issue of
trying to communicate not only to the patient but also to the surgeons
what we really mean by accommodation. The labeling should reflect the
fact that the sponsor has failed to provide conclusion evidence of a
mechanism of action.

There is clear evidence that this lens will not eliminate the need for a
reading add in about half the eyes. The labeling should reflect this to
prevent patients thinking that the lens will provide them with both a
near and a distance correction.

Issue of safety. It seems pretty safe. On that point I will finish.

CHAIRPERSON WEISS: Thank you very much, Dr. Bradley. My apologies for
not allowing you adequate time to finish your last slide.

We are going to \-- actually, since we are moving along at a good clip,
we are going to begin with the panel discussion. This may continue after
lunch. We will probably break for lunch between 11:45 and 12:00.

With that said, we are going to start question by question. Would I be
able to ask the FDA if they could have their questions put up there
again so we can use this as a format to discuss this PMA.

While the agency is putting that up, I\'ll just start by verbally giving
the panel the first question and then we can start the discussion before
it gets put on the slide.

Question No. 1. This is the first IOL that proposes accommodation as its
mechanism of action. This is a two-parter.

a\) Do the effectiveness data support a claim of accommodation?

b\) What performance issues should be considered both generally and for
product labeling?

We\'re going to start with a). To the panel, do the effectiveness data
of this PMA support a claim of accommodation?

Dr. Coleman, why don\'t we work our way around.

DR. COLEMAN: Well, after being educated by Dr. Bradley in terms of how
he was looking at accommodation, I would say yes, it does support a
claim of at least one diopter of accommodation based on his estimates.

CHAIRPERSON WEISS: I think we\'ll use the format of sort of working our
way around if no one individually has a comment on this.

DR. HO: No comment.

CHAIRPERSON WEISS: No comment. In a vote we\'ll call that an abstention
and in discussion we\'ll call it a pass.

Dr. Matoba.

DR. MATOBA: Pass.

CHAIRPERSON WEISS: Dr. Bradley.

DR. BRADLEY: I get to go again? This is great.

CHAIRPERSON WEISS: Encore. Encore.

DR. BRADLEY: This is great.

DR. HO: You get my time now, Arthur.

DR. BRADLEY: Thank you very much.

DR. LEPRI: Not with all the slides, though.

DR. BRADLEY: My other 47 slides are right here. Go get your sandwiches
now. You\'re going to need them.

Okay. Boy. I wish it were simple, you know. I think you got a sense from
my presentation the frustration in trying to review a product that
claims to provide accommodation with such a minimal data set providing
indication of accommodation. That\'s a very frustrating situation to be
in. I think one that we hope never to be in again. Let\'s summarize that
again.

The objective autorefractive data, the biometry data both indicate
between half a diopter and one diopter of accommodation. However, this
is pharmacologically induced, not accommodation in response to a near
target.

The most subjective data set was the near over refraction. This is data
that is provided under non-pharmacologically induced conditions of
natural viewing and it very clearly seems to show about one diopter of
accommodative amplitude.

I think Dr. Glasser had a very nice slide of that, those two histograms
showing the difference between the two lenses. I think those in the end
were the most compelling data set for me.

The other data set that seems compelling is the intermediate acuity data
through the distance correction. Intermediate acuity was basically
20/20. For the standard IOL group this was not the case.

Again, those data seem to point to about 1 or 1 and a quarter diopter of
accommodation. In the end we are left with rather incomplete data but
what am I going to come down, one diopter or a half diopter? I\'ll saw
about 1 plus or minus a quarter.

CHAIRPERSON WEISS: So you would support that it does \-- the
effectiveness data does support a claim of approximately a diopter of
accommodation?

DR. BRADLEY: Correct.

CHAIRPERSON WEISS: Dr. Matoba.

DR. MATOBA: Well, having passed initially, but I have a question for Dr.
Bradley. The psychoplegic and the biometric data, the end was small and
then you say that you have some concerns about the pupil size.

You say that the most compelling data would be the larger and the
greater body of data regarding the over refraction over the best
corrected distance. But if the starting point for that is a manifest
refraction that was not standardized, how comfortable are you with that
data?

DR. BRADLEY: I think failures of standardization as a great way to
introduce noise into your data set. The noise with such a large sample
size should not have affected the mean very much. I guess I\'m not so
concerned about that.

CHAIRPERSON WEISS: Dr. McMahon.

DR. McMAHON: With regard to that point a), I think I\'m going to vote
no.

CHAIRPERSON WEISS: Can you \-- because of discussion can you give us
your reasons?

DR. McMAHON: Sure. Dr. Bradley has actually stipulated the majority of
my points so I won\'t review all of them. Really all the objective
evidence is all under extreme circumstances with the psychoplegic and
pilocarpine. Even though the extreme circumstances we have objective
evidence to maybe a half a diopter, one diopter if you go to the
extreme.

All the rest of it is very circumstantial and could potentially be
explained by pupil size issues, refractive issues. For example, if the
examiners are instructed to push plus through in the refraction, you can
account for all these differences at this point since we\'re talking
maybe and half to one diopter.

This is a revolutionary period. This is a revolutionary device. I think
the standard needs to be set that the individual or companies or
sponsors need to demonstrate objectively that if they have a new process
that they prove that that process really exist and I don\'t think they
have met that requirement.

CHAIRPERSON WEISS: Just as a follow-up question, how would you propose
that that get done and what form would you like for that to get done?

DR. McMAHON: There are a variety of psychophysical methods that probably
Dr. Bradley could comment on more objectively without much difficulty. I
think if they demonstrate that in a follow-up study, then I would be
much more comfortable believing that this truly demonstrates an
accommodative effect.

CHAIRPERSON WEISS: So you might be interested in a postmarket study?

DR. McMAHON: Postmarket is probably not what we are talking about here.
Almost like an ancillary study of relatively small number. There are
methods that can be done.

CHAIRPERSON WEISS: Dr. Young.

DR. YOUNG: I abstain.

CHAIRPERSON WEISS: Dr. Grimmett\>

DR. GRIMMETT: No comment at this time.

CHAIRPERSON WEISS: Mr. McCarley.

MR. McCARLEY: I just had one comment. That is, the definition of a
standard IOL that Dr. Bradley was bringing up. I am just curious what is
a standard IOL? I would say in what I\'ve seen here is that there is
accommodation of some level but that is not to say other devices don\'t
provide some level of accommodation.

Maybe relative to what you are defining as a standard IOL or whatever
the control group was, I would agree that there is a difference.
Probably measurable but I\'m not sure whether you could say that overall
IOLs would have an advantage.

CHAIRPERSON WEISS: Ms. Such.

MS. SUCH: I pass on this question.

CHAIRPERSON WEISS: Well, we don\'t have consensus and the majority of
the people are passing. I would sort of like to get some feeling if we
had to put it to a vote at this point under this particular question how
many would vote for an effectiveness data supporting a claim of
accommodation and how many would not.

Dr. Bradley, do you have a comment?

DR. BRADLEY: I don\'t know whether this is appropriate or whether it\'s
a clarification issue. Imagine that we had a product with extremely
solid data indicating half a diopter of accommodation. Would we consider
that effective accommodation or is the problem here that the data is
inclusive, although suggestive, of accommodation? Do we have a problem
here because of the quality of the data or the magnitude of the apparent
accommodative effect? Either could be considered ineffective.

CHAIRPERSON WEISS: How about if I rephrased a) and said do the
effectiveness data support a claim of one diopter of accommodation?
Would you be comfortable with that?

DR. BRADLEY: Yeah, I think that might clarify the issue.

CHAIRPERSON WEISS: Let\'s make that the new a). Is that okay with the
agency if we said it that way?

DR. LEPRI: Yes.

DR. ROSENTHAL: You can say anything you want.

CHAIRPERSON WEISS: That\'s why I like working with these folks.

Dr. Bradley.

DR. BRADLEY: Just to make a comment on Tim McMahon\'s point regarding
postmarket study.

CHAIRPERSON WEISS: Actually, those were my words. I think he was more
interested in something earlier than that.

DR. BRADLEY: Well, perhaps I\'ll comment on Jayne\'s words then. Yeah, I
think Tim McMahon is right. This is not an issue to be studied in a
postmarket environment. What is missing here is not more clinical data.
We\'ve got lots of clinical data.

What is missing is some really hard core lab scientific data showing
that the product does what it claims to do so we\'re talking about
getting five people in the lab somewhere in this country or elsewhere
where they can actually measure accommodation and measuring
accommodation.

This is not a huge postmarket issue. It\'s a very focused study in the
lab providing data that will generally be accepted as evidence of
accommodation.

CHAIRPERSON WEISS: Dr. Rosenthal.

DR. ROSENTHAL: It becomes postmarket if the FDA and the company and the
panel agree that the lens is relatively safe and effective for the
treatment of aphakia for certain indications and the claims are worked
out in the postmarket arena. It depends on what the company and the FDA
and the panel feel about what should be said.

CHAIRPERSON WEISS: I think what we will be able to \--

DR. ROSENTHAL: Have I made myself clear to you? I mean, if you feel
it\'s not safe and effective under any circumstances, well then it\'s
not safe and effective. If you feel it\'s safe and effective for the
treatment of aphakia with improved near blah, blah, blah, but the
mechanism is uncertain, then you can recommend that be done either pre
or postmarket.

The company and the FDA can then decide whether they want to make that
determination premarket or postmarket. The claim issues can be decided
postmarket.

DR. HO: I would just echo some of those comments and expand a little
bit. From my standpoint the issue of accommodation is very muddled.

I actually discounted that issue in evaluating this because I view my
charge here and the definition of effectiveness is defined as reasonable
assurance that in a significant portion of the population use of the
device for its intended uses and conditions of use when labeled. I think
that is an issue here, will provide clinically significant results.

If you ask me if the dataset of this small number of five to 10 shows
evidence for accommodation I would vote no. In terms of clinically
significant results, which I think is relevant in our charge here, I
think that is the more relevant question. I think it is pretty
compelling.

CHAIRPERSON WEISS: Dr. Coleman.

DR. COLEMAN: Maybe change the question to, \"Did the effectiveness data
support a claim of one diopter of functional accommodation.\"

DR. HO: I\'m comfortable with that terminology \"functional
accommodation.\"

CHAIRPERSON WEISS: Would the agency be comfortable with that
terminology?

DR. ROSENTHAL: Whatever the panel makes a recommendation.

CHAIRPERSON WEISS: If we changed a) Did the effectiveness data \--

Dr. Lepri.

DR. LEPRI: Pardon me, Chairman. Essentially that issue of one diopter of
functional accommodation is addressed by Part B, what are those
performance issues. Say is there accommodation and then Part B they are
saying how much and you\'re going to put the limits on it by your
recommendation so it\'s not really changing Part A so that is
acceptable.

CHAIRPERSON WEISS: Dr. Bradley.

DR. BRADLEY: Given Dr. Glasser\'s comments and my own comments, I am
reluctant to invent new terms here. I would discourage the panel from
adopting new terminology, although it is seemingly reasonable in this
environment.

Functional accommodation sounds reasonable but, please, let\'s not do
that. We know what we\'re talking about here. Do we have accommodation
or do we have visual quality over the dioptic range? I mean, we can be
descriptive. We don\'t need to add new terminology to this already
muddled field.

CHAIRPERSON WEISS: So if we address question 1 by saying that do these
effectiveness data support the claim of one diopter accommodation, could
I have just a preliminary vote if the panel members, how many panel
members would agree with that at this point? Dr. Bradley wants me to
restate that. So we have Dr. Coleman, Dr. Matoba \--

DR. YOUNG: Is this functional?

CHAIRPERSON WEISS: No. We\'ve taken out the terminology. I have deferred
to Dr. Bradley\'s sensibilities and we have taken out the word function.
We\'re just going to be talking straight accommodation.

If we state that, \"Do the effectiveness data support a claim of one
diopter of accommodation,\" we started on that side. Dr. Coleman said
yes, Dr. Matoba said yes, Dr. Bradley said yes, Dr. Grimmett said yes.
Those are four yeses.

How many would disagree? Dr. McMahon, Dr. Young, and Dr. Ho would
disagree. No one abstained on that one. That\'s good enough for me. I\'m
sure the sponsor would agree with that as well.

Dr. Lepri, did you want anything else on that first issue or can we go
on to question No. 2?

DR. LEPRI: That\'s fine, except are you going to address \--

CHAIRPERSON WEISS: Yes. Thank you. Aside from talking about the amount
of accommodation, what other performance issues should be considered
both generally and for product labeling? This is, I assume, going to be
a longer portion of the discussion.

Product labeling and performance issues. I think you had addressed some
of these, Dr. Coleman.

DR. COLEMAN: Some of them.

CHAIRPERSON WEISS: Maybe you could just restate the ones that you have
addressed and we could bring them to the panel for discussion.

DR. COLEMAN: I guess in terms of including the less than or equal to
plus or minus half diopter change in the MSRE over a year for the
stability data of the near acuity and also the intermediate acuity.
That\'s a performance issue.

CHAIRPERSON WEISS: Could you mention the labeling suggestions you had
that \-- well, I guess that would be \-- are you referring to all
labeling or basically as it relates to accommodation.

DR. LEPRI: As it relates to accommodation. There is a subsequent
question.

CHAIRPERSON WEISS: As relates to accommodation could you give us your
recommendations again, Dr. Coleman?

DR. COLEMAN: As it relates to accommodation?

CHAIRPERSON WEISS: Yes, specifically.

DR. COLEMAN: One thing that could be included in the labeling that
approximately 50 percent or 57 percent of patients did not need a near
add when reading the newspaper and that would relate to information to
the surgeon in terms of the use of this lens can subject functionally.

Dr. Bradley, would you want to address that question as well in terms of
relating to accommodation or any other labeling?

DR. BRADLEY: I think the labeling is the tricky point. I think the
sponsor would like to, and we have already seen from their provisional
information they gave us on labeling or description to the patient that
this is a lens that provides as the conclusion said, clear vision from
distance to near.

Well, quite frankly, it does not and I think that would be very
misleading to put that on the labeling. The sponsor would also like to
be able to communicate that this is a lens that achieves accommodation
by anterior movement.

I think it\'s important to be clear that they have never shown that, in
fact, this lens moves anterially during near work. I think it would have
been great if they had had those data because that would make for a very
compelling marketing material it seems to me.

Again, I don\'t think they have those data so it\'s hard to make that
claim in labeling. Really those are the two main labeling issues that I
see.

CHAIRPERSON WEISS: Could you restate those again sort of succinctly or
anything that you would suggest?

DR. BRADLEY: Jayne, you\'ve been working with me long enough to know I
can\'t do anything succinctly. I\'ll try. The claim that this product
provides clear vision at near is a misrepresentation of the data and
should not be included in labeling.

CHAIRPERSON WEISS: That\'s fine. I\'m just wondering was that claim made
in the patient or the physician labeling? It doesn\'t really matter.

DR. BRADLEY: I can\'t recall. It was the summary statement of their
presentation this morning so you know it\'s going to appear somewhere.

DR. COLEMAN: I don\'t think it was in the physician\'s labeling. I
didn\'t see it in the patient.

CHAIRPERSON WEISS: We are going to have to address both the physician
and the patient later on.

DR. ROSENTHAL: Madam Chairman, Rosenthal.

CHAIRPERSON WEISS: Dr. Rosenthal.

DR. ROSENTHAL: The agency can work with the company on the details of
the labeling as long as the panel provides the overview of what the
issues are. I think it\'s clear that representing the results of the
study might be better than representing some definitive statement about
the performance of the lens. Is that right, Arthur?

DR. BRADLEY: I would concur with that completely and with only one word
of warning, that the central issue in this entire discussion is
accommodation and we have already established that there is considerable
uncertainty about what we are, in fact, talking about. This is not a
trivial point. The labeling will be very tricky.

One has to be \-- as you are suggesting, the sponsor has to accurately
reflect the data, but also be able to communicate these data in a way
that is meaningful to both the physician and the patient. It is clear
because of this problem of what people mean when they say accommodation.
This is going to be a challenge.

CHAIRPERSON WEISS: I would suggest, and I would be interested in the
opinions of the panel to include the table where they had actual
functional items that patients could do reading, needlework, etc., and
include that in the patient as well as the physician labeling. That
would bespeak specifics as opposed to generalities. I don\'t know what
the panel thinks.

Glenda Such.

MS. SUCH: Yes. Hi. This goes across both types of labeling. I have a
concern. I wanted to mention at the beginning of this that earlier I had
heard from the FDA saying that at this time perhaps we should leave the
labeling. I think that this panel really needs to be able to discuss
labeling issues all the time.

The other issues is about the accommodations and with looking at the
clarity issue because of the functional implications of not being able
to read newspaper print and that what most people think about if they
are going to be able to be told that their images are going to be clear.
That is usually their standpoint, not something else. They are not
thinking that they are going to have to use any type of spectacles. Even
in the labeling that does exist that I have been reading so far, I have
been seeing that it talks about all three distances without spectacles
so that needs to be, I think, very clear.

CHAIRPERSON WEISS: Thank you.

Dr. Ho.

DR. HO: My guidance \-- my recommendations for issues to consider in
labeling would be \--

CHAIRPERSON WEISS: Actually, I\'m just going to clarify this. On
question three we\'ll be specifically talking about all sorts of
labeling. For this question we\'re speaking about labeling that is
specifically related to the accommodation.

DR. HO: Okay. From my perspective and from the standpoint of evaluating
this new product, I\'m thinking about it in terms of visual performance.
I think accommodation or mechanisms of accommodation are secondary.

I\'m actually not sure that any postmarket study may actually establish
what the mechanism is because there are multiple mechanisms of action
that may not be relevant for an individual eye that\'s tested. But for
me the acid test is function. I like the idea of including that table.

That speaks to what the patients can understand in terms of near vision,
reading the newspaper, intermediate vision, seeing something on a
grocery shelf, as a way for them to translate this as a way to assess
reducing the need for spectacles.

I think the other issue is you have to view reducing the need for
spectacles compared to what implying perfect vision with spectacles is
one issue and implying pseudophake with spectacles is another issue.
From the standpoint of improvement in our technology, I like the product
and I would like to see that spelled out in a way that a patient can
understand.

CHAIRPERSON WEISS: Just a couple of points there. One is I think we
would all agree it\'s not the sponsor\'s job to figure out mechanism,
but it is their job to support a claim so if their claim is one of
accommodation and they have to show accommodation as far as how that
happens, it\'s up to someone else if they are interested to figure that
one out.

DR. HO: Hence, my recommendation to eliminate that word.

CHAIRPERSON WEISS: Accommodation? Well, that\'s a claim so this is
something the panel must determine whether or not we support the claim
of accommodation. What the mechanism for that claim is the sponsor does
not have to tell us.

The second thing is just because I have asked Dr. Coleman to kindly
describe for the labeling issues, I would point out that it sounds like
there may be some consensus that the bilateral patient survey activities
without spectacles is table 10.5. I think that is something that we will
talk about having for the patient as well as the physician booklet.

Dr. Bradley and then Dr. Matoba.

DR. BRADLEY: Is it okay for me to ask the sponsor to step up and answer
a question on this particular issue? I need some clarification on that.

CHAIRPERSON WEISS: Yes.

DR. BRADLEY: I have a question about the survey, by the way.

CHAIRPERSON WEISS: If you could just identify yourself when you come to
the podium.

DR. GORDON: Judy Gordon.

DR. BRADLEY: Hi, Judy.

DR. GORDON: I may need to get the data but I\'ll try to answer.

DR. BRADLEY: I think as I mentioned, 57 percent reported that they could
read the newspaper without spectacles. I think we had 30 some could sew.

PARTICIPANT: 38 percent.

DR. BRADLEY: I don\'t know 38 percent of anybody who sews anymore, so it
occurred to me that I was misinterpreting those data.

CHAIRPERSON WEISS: I think it was of the patients who attempted to do
that, 38 percent could do that.

DR. BRADLEY: That\'s what I wanted a clarification on.

DR. GORDON: Patients were allowed to note the response to those items
which they believed were pertinent which is why some of the survey data
we presented have varying ends. For example, patients who didn\'t use a
computer simply didn\'t comment on that.

DR. BRADLEY: Okay. Thank you.

CHAIRPERSON WEISS: Unless you were going to add that to your claims that
this would allow you to do these added activities.

DR. GORDON: I don\'t think that\'s the plan.

DR. BRADLEY: Thank you.

CHAIRPERSON WEISS: Dr. Matoba.

DR. MATOBA: In the labeling it says almost all patients implanted in
both eyes with the CrystaLens had good distance vision after surgery and
could see 20/32 or better at distance, i.e., see 20/32 or better at
distance. I think that rather than saying almost all, I would prefer to
see the percentages. I guess if you put that table in as you suggested,
that would help. I think they should point out that the results were not
as good if only eye is implanted.

Then later they say the majority of patients could read the paper
without glasses. Then the next sentence says almost all study patients
could apply makeup, shop, blah, blah, and read a paper without glasses.
That second sentence seems to imply that almost all patients could do
all of those activities and that\'s a bit misleading. That\'s not true.
I think they need to be a little bit more accurate and possibly
percentages regarding specific tasks.

CHAIRPERSON WEISS: I think Dr. Matoba is looking at attachment to draft
brochure for the C&C Vision CrystaLens model and the clinical study
results benefits in the last sentence, which I also had a problem with,
that almost all the study patients could pass their driver\'s test.

I wondered could they pass their driver\'s test before this and does
this allow you now to learn how to drive. I think we might have to
rescribe that particular \-- in fact, maybe we should just eliminate
that and just put the amount of people, the actual table 10.5. Would you
agree with that?

DR. MATOBA: Yes.

CHAIRPERSON WEISS: I see agreement, Dr. Ho, Dr. Matoba. Dr. Bradley is
raising his hand. Yes.

DR. BRADLEY: A lot of that table appears very \-- provides a very
optimistic view of the product. We get these very high percentages. The
whole point \-- the novel point of this product is that it provides good
near vision. There are only a couple of items in there that really
address the issue of near work.

In a long table like that, there at the bottom by the way, they could
easily be lost after you\'ve seen all these 95 percents. I think if the
table is going to go in there, I think some sort of emphasis of the near
work survey questions should be made.

CHAIRPERSON WEISS: Do you have this?

DR. BRADLEY: I do.

CHAIRPERSON WEISS: I\'ll just read it out and as long as we are
addressing this issue, maybe we can finish up with this point and then
break for lunch.

The sentence that Dr. Matoba was referring to, and I\'m also speaking
about, reads, \"Almost all of the study patients could pass their
driver\'s test, could see their computer, shop, or apply their makeup,
and could read a newspaper without glasses or contact lenses.\"

I would ask if anyone from the panel could wordsmith this particular
sentence which could convey more accurately that there was improved near
vision but that if you were doing something that was extremely up close,
you probably would need glasses.

Dr. Bradley.

DR. BRADLEY: Yeah, I think I would follow Ralph\'s suggestion that we
don\'t wordsmith it but we let the FDA realize that sentence if it is
going to appear in this product description, it must accurately
represent the data. My personal add is to ensure that the near work data
be emphasized because that is the novel claim of this particular
product.

CHAIRPERSON WEISS: So would it be satisfactory to the agency if the
panel then just suggested that the physician and the patient labeling
indicate there was improved near vision with this lens but certain tasks
still would require some glasses in a percentage of patients?

DR. ROSENTHAL: If that is what the panel would like to recommend.

CHAIRPERSON WEISS: I\'ll put that to the panel. Is that what the panel
would like to recommend?

ALL: Yes.

CHAIRPERSON WEISS: So I hear actual consensus on this one which means it
is probably time for us to break. I\'m going to let the panel know that
we are having a meeting in the hotel\'s private dining room so I would
like everyone from the panel to meet there. We are going to be breaking
one hour for lunch so if everyone could be back here promptly.

EXECUTIVE SECRETARY THORNTON: Yes. This is not anything to do with the
PMA that we are discussing now. This is a presentation that FDA has
planned for you on a totally different matter.

CHAIRPERSON WEISS: So we are adjourned for lunch.

(Whereupon, at 11:55 a.m. the meeting was adjourned for lunch to
reconvene at 1:00 p.m.)

A-F-T-E-R-N-O-O-N S-E-S-S-I-O-N

1:14 p.m.

CHAIRPERSON WEISS: I would ask all the panel members to take their seat.
We are going to begin the afternoon session. Sally Thornton has an
announcement.

EXECUTIVE SECRETARY THORNTON: Something to add to the updates for the
Diagnostic and Surgical Devices Branch that just came in hot off the
press.

On May 23, 2003, we approved P930016 Supplement 16 for the Visics Star
S4 Wavescan indicated for wavefront guided Lasik for the reduction or
elimination of myopic astigmatism up to minus six diopters MRSE with
cylinder between 0.00 diopters and minus three diopters at the spectacle
plane. That\'s the end of the announcement. Thank you.

CHAIRPERSON WEISS: I would ask the FDA if they could put their questions
back on the screen so the panel could proceed through those questions
again.

I think we finished off with the first question unless anyone has any
other comments. Seeing no comments, we\'ll go on to the second question.

2\. Do you believe that the sponsor has demonstrated the stability of
the hinge, and therefore the stability of the accommodative refractive
effect?

Dr. Coleman.

DR. COLEMAN: Well, in my review I felt that the long-term stability
evidence had not been established beyond at least 10 years if you
believe in flexibility of the lens. And then in terms of more than one
year in terms of the clinical data that they provided.

CHAIRPERSON WEISS: Do you want to say 10 years?

DR. COLEMAN: I think we had suggested \--

CHAIRPERSON WEISS: Do you just want to say long-term stability has not
been established?

DR. COLEMAN: Yeah, I think that was what we had kind of \-- because also
that came from Dr. Bradley\'s review also was a recommendation in terms
of having it on the labeling indicating that long-term stability had not
yet been established.

CHAIRPERSON WEISS: Do you think it would be important to differentiate
between the stability of the hinge and the stability of the
accommodative refractive effect to indicate that the long-term stability
of neither of those issues had been established, or would you like to
lump them?

DR. COLEMAN: I think for the stability of the hinge they have shown some
stability of the hinge up to a million cycles whatever that applies to
clinically in terms of movement of the lens. In terms of the
accommodative ability clinically based, that was only up through the
one-year clinical trials so you could divide them up.

CHAIRPERSON WEISS: So you would like to basically add something and, if
I may speak for you and if I am incorrectly representing you, please let
me know.

DR. COLEMAN: I will.

CHAIRPERSON WEISS: You would like to add something saying that long-term
stability has not been established for the hinge or the accommodative
refractive effect. Any other comments on this issue?

Dr. Bradley. We wait with baited breath.

DR. BRADLEY: I was curious about what we might anticipate if the lens
hinge failed or started to fail. It seemed to me that the hinge might
become weaker and potentially get more accommodation out if the hinge is
providing any resistance at the time it goes in. I\'m not sure a partial
failure is a bad thing in this particular device.

It might actually enhance its effectiveness. Presumably what we are
looking for is a major mechanical failure of the hinge in which the lens
becomes unhinged and then presumably it\'s then dangling somewhere
inside the eye and of little optical value.

I was just going to say that in terms of the catastrophic event it seems
pretty clear that a million of these movements forward and backwards
seems to provide no noticeable damage to the lens. As I said in my
review, because we haven\'t seen actual evidence that the lens is moving
during near and distance work, then we are not sure whether a million
cycles is adequate or inadequate at this point. That\'s the problem.

CHAIRPERSON WEISS: I would also ask the panel if they think it would be
possible, say, if there was a hinge failure at a certain number of
cycles might one portion of the hinge be damaged earlier than the other
and the lens now go into an oblige angle or rub against the iris.
Personally I don\'t think we have any information on this but I would
ask the panel for their comments on that particular issue.

DR. BRADLEY: I think in terms of \-- this is Arthur Bradley. In terms of
labeling, I think, again, state the data. A million movements. No
visible damage to the hinge. One year after implantation seems to work
as well as it did just after it was implanted. At this point that\'s all
we have.

DR. COLEMAN: So we have no information on what happens if one of the
hinges doesn\'t work and the other one does so you have an oblique.

CHAIRPERSON WEISS: I think we will still go back to what you were
suggesting, long-term stability of the hinge has not been established.
Long-term stability of accommodation has not been established.

Dr. Rosenthal.

DR. ROSENTHAL: Rosenthal. Do you think it might be reasonable \-- what
do you think would be reasonable to include in labeling about the
potential for one hinge? Do you think it should be mentioned or do you
think it should not be mentioned at all?

CHAIRPERSON WEISS: Are you addressing this to the panel or to me?

DR. ROSENTHAL: To the panel. As a remote possibility.

DR. COLEMAN: I think it would be important to mention it as a remote
possibility so that the surgeons can mention it to the patient that this
might potentially happen. Although the effect on the patient\'s acuity
with an oblique situated lens is not established.

CHAIRPERSON WEISS: Dr. Matoba and then Dr. Bradley.

DR. MATOBA: Actually, I wouldn\'t mention it because we have no
information that would ever happen so it is so theoretical that I would
not mention it.

CHAIRPERSON WEISS: Dr. Bradley.

DR. BRADLEY: I think panel speculations should not be part of the
labeling.

CHAIRPERSON WEISS: Dr. Grimmett.

DR. GRIMMETT: Dr. Grimmett. I similarly would not mention it speculating
on what might happen when we have no evidence that it will happen is not
proven.

CHAIRPERSON WEISS: Dr. Matoba.

DR. MATOBA: And also I would not say that after million excursions there
was no noticeable damage because I think that is misleading. They may
think, \"Oh, it\'s way beyond my lifetime,\" but we don\'t know that. It
could be a year or less. I would just say long-term stability has not
been demonstrated.

CHAIRPERSON WEISS: Dr. Bradley and then Dr. Young.

DR. BRADLEY: I will reiterate how easy it would have been to answer this
question if the sponsor had provided us with dynamic measurements of
refraction during normal distance and near fixation because we would
have seen, in fact.

If the lens was oscillating, we can estimate \-- make some sort of
estimates about how many times this lens is going to flex over a certain
period of time. At this point we really don\'t know because we have no
data.

CHAIRPERSON WEISS: Since you introduced that subject, I will take rest
from this question a little bit and ask whether you then would want some
ancillary studies or you do not feel they are necessary for approval of
this?

DR. BRADLEY: It seems to me the sponsor could have much more compelling
arguments in favor of this product to be included in the physician\'s
and the patient\'s information if they did a study showing that the lens
actually moved as designed to move. That is from their perspective.

From our perspective as long as the claims do not claim how they think
the lens works but the fact that they don\'t have actual evidence that
it works that way, I think they are fine. I don\'t think that affects
approval. It just affects what claims they can make.

CHAIRPERSON WEISS: But you are still comfortable with the claim of
accommodation of one diopter without that extra data?

DR. BRADLEY: Yes.

CHAIRPERSON WEISS: Fine.

Dr. Young.

DR. YOUNG: I was just going to mention that I concur with not mentioning
hinged dislocation or optic dislodgment or oblique angle. The only way
we can really study that is if we have histopathologic studies of actual
hinge integrity. That\'s obviously not going to be the case for this.

CHAIRPERSON WEISS: Would anyone want to put in the labeling regarding
long-term stability that the lens has only been studied for a period of
time that it\'s been studied?

DR. COLEMAN: What do you mean?

DR. SLADE: What was that question again?

CHAIRPERSON WEISS: For a year or two.

DR. HO: Allen Ho. I would just say that we can say very little. I mean,
what\'s of relevance is the visual function overtime. I think a claim
that stability of visual function to the endpoint that they showed is
reasonable but beyond that I would say it\'s unknown and that\'s what\'s
relevant.

CHAIRPERSON WEISS: So are we still at accommodative stability and hinge,
those two words?

DR. HO: I have no problem with omitting hinge. I don\'t think people
care about hinge. I think they care about how they see.

CHAIRPERSON WEISS: I personally would care about the hinge only because
I\'m concerned if the lens did dislocate not only would it affect vision
but it could cause iritis or something like that. I would prefer to keep
that in there. It might not have relevance but I would prefer to keep it
in there.

Dr. McMahon.

DR. McMAHON: Tim McMahon. The data suggest that visual acuity or visual
function is stable at one year. I don\'t think we can actually say much
more beyond that which is sort of echoing what Dr. Ho is saying.

I don\'t think that we can say this has anything to do with stability of
the hinge because we don\'t really know whether the hinge is moving at
all. We have some suspect or suggestive information might be moving a
little bit, but at the same time one can make the argument it\'s really
not moving hardly at all anyway.

Arthur made the suggestion that we not speculate in terms of various
different functions of this lens and I agree with that. I think the
information should be limited to what the data support and that is that
visually acuity is stable. There are different differences at a one-year
period.

CHAIRPERSON WEISS: Just in terms of the last comment you just made and
the patient labeling, there is something that states CrystaLens moves
backwards and forwards. Is that something that you would want taken out
of there? How does the panel feel about that? I don\'t want to go
sentence by sentence but just because you brought that up.

Dr. McMahon.

DR. McMAHON: There was going to be a point that I suggested that be
removed from the labeling.

CHAIRPERSON WEISS: Good time to make that point.

Dr. Bradley.

DR. BRADLEY: Again, perhaps for clarification, it might be adequate \--
acceptable to say that the lens is designed to move forwards and
backwards and, in fact, it can do this. Sort of a bit of wordsmithing
there but it never shown it doing this in the circumstances in which it
was intended to be used.

That is a shortcoming that the sponsor has to deal with. If I could put
myself in the sponsor\'s shoes, I would rush out and do that right away
because I would like to make that claim, but without the data I\'m not
sure they can make that claim at all.

CHAIRPERSON WEISS: Forgive me, Ralph, because I know you don\'t want to
go through sentence by sentence but there is \--

DR. ROSENTHAL: No, that\'s fine to pick up areas that you want to
discuss.

CHAIRPERSON WEISS: In the patient labeling it says as stamped, \"The
CrystaLens moves backwards and forwards inside the eye at the brain\'s
command to focus the lens to provide distance, intermediate, and near
vision and reduce your need for glasses or contact lenses after
surgery.\" What does the panel think about that sentence? Are you
comfortable with that sentence?

Dr. Bradley.

DR. BRADLEY: I guess I\'m not so comfortable with it. I think \-- I\'m
just going to repeat myself.

CHAIRPERSON WEISS: Rather than repeating yourself can you give me \--
not that I mind listening to your repetitions but can you give me an
alternative or suggestion for the labeling that would answer what your
concerns are?

DR. BRADLEY: Certainly a recommendation would be \-- recommendation to
the FDA would be to require the sponsor to actually show that is true
prior to putting that in the labeling.

CHAIRPERSON WEISS: Fine. So just eliminate it from the labeling. That\'s
easy. Any other thoughts on that particular issue?

DR. McMAHON: This is Tim McMahon again. I would concur.

CHAIRPERSON WEISS: Dr. McMahon concurs. Any other discussion?

Dr. Ho.

DR. HO: Yeah, I\'ll wordsmith it. I would say that the CrystaLens with
respect to that attachment sentence that you\'re speaking to, the
CrystaLens simply reduces your need for glasses or contact lenses for
intermediate and near vision after surgery.

CHAIRPERSON WEISS: I think basically you are agreeing let\'s take out
\-- suggest that mechanism of moving backward and forward be removed. I
think this would then lead us into question No. 3 unless there are any
other comments on question No. 2.

Question No. 3. Does the panel recommend any other modifications to the
proposed physician or patient labeling?

We have at this point discussed about the issues about the
accommodation, the issues about the movement of the lens and the
stability of the hinge and the stability of the accommodative refractive
effect. I would add personally that perhaps we should indicate that the
visual results may not be as good if only one eye undergoes the
implantation. I see some agreement by Dr. Ho and Dr. Young.

Dr. Matoba, you have a comment?

DR. MATOBA: I think we mentioned that under when we previously discussed
labeling and I agree.

CHAIRPERSON WEISS: What other labeling issues \-- actually, this would
be the point, Dr. Coleman, if there are other labeling issues, you could
bring those up, and we\'ll go to Dr. Matoba and Dr. Young and then Dr.
Grimmett in that order.

Dr. Coleman.

DR. COLEMAN: One was to aim to plano instead of minus half sphere. The
other was to include the information on the stability of near acuity and
intermediate acuity and distance acuity in the physician labeling.

The other one was a warning precaution, the effect and performance of
the lens is unknown. Another is to include Table 10.3 from the patient
survey on the frequency that subjects wore the glasses.

CHAIRPERSON WEISS: Is that Table 10.5?

DR. COLEMAN: 10.3. 10.5 has already been recommended.

CHAIRPERSON WEISS: So we\'ll have 10.3 and 10.5.

DR. COLEMAN: That\'s page 150 of 195. It is, \"How often do you wear
spectacles during waking hours.\" \"I do not wear spectacles\" in 26
percent. \"I wear spectacles almost none of the time\" in about 48
percent. That table.

CHAIRPERSON WEISS: Okay. 10.3 and 10.5.

DR. COLEMAN: Mention as precaution the range of the axial lengths and
lens powers that were used in the study. Mention on page 2 of the
physician labeling that atropine should be given immediately
post-operating and post-operative day one. Include under adverse events
the possible increased rate of CME associated with sulcus-bag placement
of haptics. And then other issues that came up for physician labeling.
Do you want those?

CHAIRPERSON WEISS: Yes, please. As we go around, just give me every
labeling concern that you have.

DR. COLEMAN: These are from everybody. Mention that the accommodative
amplitude appears to be about one diopter or less. Mention that the
mechanism of action is hypothetical, that it\'s a hypothetical mechanism
of action that hasn\'t been proven yet in terms of the claims in the
studies that have been done.

Then we also had recommended to mention in both the physician and
patient labeling table 10.5 and emphasizing that 57 percent of patients
do not need a near add to read the newspaper meaning that 43 percent do
need to use a near add. Another suggestion \-- I did not see clear
vision mentioned in any of the physician or patient labeling but make
sure that is not \--

CHAIRPERSON WEISS: Actually, the sponsor mentioned to me in the break
that was only included in the presentation of the sponsor. It was not
included in any of the written materials so we can actually take that
out of the equation.

DR. COLEMAN: Okay. In addition, include Table 10.5 in both the physician
and patient labeling and make sure that you emphasize the near work on
Table 10.5.

CHAIRPERSON WEISS: So perhaps another line saying, \"For certain near
visual tasks or for very close work many patients do require glasses.\"

DR. COLEMAN: Correct. And to mention in the patient labeling the
percentages of those individuals that do need glasses for near work so
not just focusing just on the newspaper information.

Then for the patient labeling we wanted to delete the clinical study
results, the last sentence. We had mentioned that, in attachment 2.

CHAIRPERSON WEISS: \"Almost all the study patients could pass their
driver\'s test.\" The sentence that begins with that.

DR. COLEMAN: Right. And then just the ones that we just mentioned about
the claims that the lens moves back and forward should be deleted
stating that the lens can be designed to do this as Dr. Bradley
suggested.

The beginning of the statement, \"At the brain\'s command the lens moves
back and forwards,\" as was just wordsmithed by Dr. Ho. Then also
including in both the patient and physician labeling that the surgical
results may not be as good if only one eye is done versus two eyes.

CHAIRPERSON WEISS: Thank you very much for that list.

Dr. Matoba.

DR. MATOBA: We should add that the lens has not been studied in patients
younger than 15. Are we going to discuss each of these points, these
suggestions?

CHAIRPERSON WEISS: Yes. This is the time to do it so if there is
anything that is suggested that you have a comment on, agree or
disagree, please let us know.

DR. MATOBA: Okay. I would disagree with the recommendation to go for
plano rather than minus half because I don\'t know about your department
but we are not that accurate and you don\'t want to overshoot and end up
with a hyperopic patient. For the first eye I wouldn\'t change that
recommendation from minus .5. I would keep it at that.

CHAIRPERSON WEISS: Dr. Bradley, did you have a comment or are we going
to go on?

DR. BRADLEY: I do have a comment but I\'m waiting for the list.

CHAIRPERSON WEISS: Dr. McMahon and then Dr. Grimmett and then Dr.
Bradley.

DR. McMAHON: I concur with Dr. Matoba\'s discussion about leaving the
surgical recommendations as is at minus half for the first eye. If
nothing else, I think that potentiates the advantages or the benefit of
this lens as is.

I want to raise a little different issue and that has to do with the age
of the patient. If for the moment, and this hasn\'t been proven to my
satisfaction, that this lens does move, we have now a revolutionary
devices that is actively doing something inside the eye rather than just
passively sitting there.

We have a trend, though not statistically significant, in their one-year
data suggesting a higher degree of uveitis and CME in these patients. I
suspect that is not going to be a completely irrelevant issue.

One of the questions I want to raise for the panel is whether we should
initially limit the age at which this procedure is done. Right now the
sponsor wants it at 18. I would actually postulate that maybe this
shouldn\'t be done on anybody under age 60 or 65 until some intermediate
term record exist.

Now, on the other hand, if the sponsor had provided information that
says, indeed, it doesn\'t move, that the near vision effects are from
some other reason, it makes my particular suggestion moot. As Dr.
Bradley has pointed out so eloquently, this particular issue hinges in
all sorts of orders.

CHAIRPERSON WEISS: The sponsor is printing the numbers now to figure out
which one would be better.

Dr. Young and then Dr. Grimmett and then we\'ll go back to Dr. Bradley.

DR. YOUNG: I had discussed earlier the issue of the YAG capsulotomy and
whether or not that has some effect on movement of the lens and had
suggested a warning or precaution that the effect on accommodative
performance of YAG plus your capsulotomy prior to 12 weeks is unknown.

The other comment was that most practices use a non-immersion method to
determine axial length. I thought a comment that immersion method may be
preferable for IOL calculation parameters for this device also be added
as a comment for labeling.

CHAIRPERSON WEISS: I would think that would be in there already. Could I
just ask the sponsor? I would assume you already have that in there that
you want immersion method to be done in physician labeling.

DR. GORDON: I\'m not sure but we certainly have the data. We\'ll confirm
and take a look but we certainly have the data to support that and it
was presented for that reason today so we are seeking input from the
panel.

CHAIRPERSON WEISS: We could add that and if it\'s in there, then it will
just be removed by agency. That\'s fine.

Dr. Grimmett.

DR. GRIMMETT: Michael Grimmett. The age comment, I\'ll just add one
thing. Dr. Matoba and Dr. McMahon already made the comment. In the draft
labeling in Vol. 1 on page 3 it does say, \"Implantation of the
CrystaLens should not be performed in patients under 18 years of age.\"
That\'s seemingly implies that over 18 is A okay. I think that somehow
needs to be revised that this study only included patients 50 years of
age or older because that particular statement implies something
different. I would definitely make sure that statement is revised.

On page 9 of 18 in the draft labeling the lens optic is listed, diopter
power 10 to 30. To the best of my knowledge the study used between 16.5
and 27.5. This may be standard practice.

The FDA expands the limit of the lens range to when they can produce
more lenses. Clearly this study did not look at 10 to 30. Again, I was
looking at the 16.5 to 27.5, I think from page 117, tab 8.5. I think
that needs to be revised.

I\'m going to make one \"get up on the soapbox\" comment and get to a
labeling issue. A major concern that I have with this lens as just a
clinician is the small optic size. A 4.5 millimeter optic is concerning
to me.

I think that senile pupillary miosis may be a protective factor here for
the older age range. I would have extreme concerns if this lens were put
in a younger subset. If their in dim illumination meets out the
conditions they had pupillary dilation to the extent that the normal
physiologic range can occur, I think they probably would have symptoms.

Additionally, a second point regarding a small lens optic. I know that
the retinal surgeons will not appreciate doing peripheral retinal
examines through a 4.5 millimeter optic lens or trying to laser a
peripheral retinal hole for lattice, or even in a diabetic patient
looking at the peripheral retina.

I think that would be difficult. I hope that sound clinical judgment
would prevail, that small lens optics are considered in patients with
retinal pathology. I do understand that the indications say don\'t
implant it in someone with retinal pathology but I think that\'s an
issue.

Lens centration on this lens with a 4.5 millimeter optic is critical.
Dr. Slade\'s comments that the lens does center exceptionally well is
reassuring, but I think that any decentration on a lens this small is a
major factor.

This will lead me into what I want in the labeling. Table 10.7 on page
153 of 195, under tab 10, Patient Survey, lists difficulty for nighttime
activities. I think with a lens optic this small, I think that is a
relevant table and I would want to see that in the labeling.

If you look at patients who had any symptom, that is, either glare
flair, difficulty driving at night, or halos at any range, mild,
moderate, or severe, a full 52 percent of patients had some symptom. If
you look at just moderate or severe of any symptom, 27 percent had some
symptom. I think that is a relevant table in a lens with a 4.5
millimeter optic. Especially if you have a patient with a large pupil.

I think that somehow in the labeling there has to be mention of that
fact either simply by including that table or stating the issue of the
effective IOL optic diameter of the pupillary plane wherever this lens
happens to sit as we discussed earlier. I think that is an issue that
does need to be made in the labeling because as a clinician that\'s what
would concern me.

CHAIRPERSON WEISS: Could I just ask you to sort of list the various
things that you would suggest as conditions?

DR. GRIMMETT: Sure. I included the ones on the labeling about 18 years
of age or older. That was number one. That was on page 3 of 18. No. 2, I
wanted the lens power range amended. It\'s listed 10 to 30 but I somehow
want to clear that the study only looked at 16.5 to 27.5. Of course, the
FDA will use prior precedent to expand the ranges they ordinarily do.

Then No. 3, at a minimum I would like to include Table 10.7 on page 153
of 195 under Tab 10 listing the difficulty for night activities. I would
like to hear other comments from the panel regarding comment about a 4.5
millimeter optic whether that type of comment in mydriasis needs to be
added. I would like to hear other opinion on that.

CHAIRPERSON WEISS: We\'re going to have Dr. Bradley and then Dr. Matoba.

DR. BRADLEY: Two main issues regarding labeling. One comes back to the
point that Mike Grimmett has just been making. The sponsor has done an
analysis indicating that a 4.5 millimeter optic is adequate.

I think the sponsor is probably correct under most circumstances in the
age group which they have used for this study. That is, 50 years and
older. I think Mike Grimmett raises an extremely important point that in
younger eyes where pupil size can be considerably larger than 4.5 and
routinely can be 7 millimeters or greater.

These young eyes installed with this lens will effectively have less
than half the area of their pupil covered by this lens. Effectively they
will be aphakic for half of the light and phakic for the other half of
the light. We all pretty much understand the consequences of that.

I think all the lawsuits that are now floating around with patients who
are treated with refractive surgery with a small treatment zone and
their pupils were larger than their treatment zone, we all kind of
understand the consequences of this mistake.

We all kind of understand the consequences of this mistake. They are
quite profound within the profession and I think that it would be
important labeling for the clinician to understand that the size of this
optic will produce problems if you fit it to a patient with pupils
larger than 4.5 millimeters.

That pretty much includes every young adult. The notion of fitting down
to age 18 I think would be disastrous for the patient and for the
surgeon who fitted it. I think Mike\'s point is extremely well taken and
one that should be clearly articulated in the physician labeling.

I would discourage the sponsor from seeking approval to have this lens
installed into eyes younger than 50 years of age. In fact, I would
recommend that prior to installing the lens some examination of the
chronic pupil size is done. Again for the same reasons that we\'ve had
had problems with refractive surgery. We do not want pupil sizes bigger
than the optical zone. This is bad news for everybody. That is the first
point. That is physician labeling.

Patient labeling. My concern here is one that I feel with this barrage
of data, indirect evidence, confusion over definitions, that patients
may not really understand what they are getting into with this lens.
I\'m wondering if there is a way to describe this product in a way that
would be clear to a patient and, therefore, would be ideal for product
claims in the patient description.

A thought that comes to mind is to point out that this lens may give one
diopter. I\'m not sure that makes sense to a patient right away from,
anyway, one diopter of extra power and, therefore, will give you clear
distance and intermediate vision but it does not provide clear near
vision.

You may under some circumstances, for example, reading the newspaper,
require a reading add. To help the product is to clarify that this is
better than you would get with a standard nonmoving IOL. The important
point is that the lens seems to provide clear vision at distance and
intermediate. It is at near that it doesn\'t provide clear vision but
the vision seems okay at near. Somehow to communicate that to the
patient so they know what they\'re getting into. With this lens they
will be able to see fine at distance.

They will be able to see fine when they are watching TV or putting on
their makeup or whatever it happens to be. But when they sit down to
read the newspaper they may need an add. Somehow to communicate that so
that the patient knows exactly what they are getting into I think would
be valuable.

CHAIRPERSON WEISS: We are going to go on to Dr. Matoba in a moment but I
just want to comment on two things. As a refractive surgeon I would say
the role of the pupil size with the symptoms is still not clear and
elucidated. But with this lens you still may want this particular
caveat.

The other thing is I would personally prefer to stay away from the word
clear. Why don\'t we don\'t talk about improved or functional so that
you don\'t need glasses. And maybe for near vision the percentage of
people will need glasses, where for distance and intermediate the vast
majority of people have excellent vision without glasses. I\'ll leave it
to Dr. Matoba to work that out for us.

DR. MATOBA: Well, my comment is that I agree with Dr. Grimmett\'s
comments. That was the thrust of my questions I asked before lunch
regarding pupil size relative to patient satisfaction and symptoms and
also the contrast sensitivity study that they did.

The sponsor said they had not stratified by pupil size patients
complaints and their function. I think if that data was available it
would be useful to see that. Then it might help us to set some
guidelines in terms of labeling for what pupil size we would not
recommend that the eye will be implanted.

Also the contrast in sensitivity of these sponsors I think said that
they had stratified that data by pupil size but I don\'t see it in this
protocol. I think they looked at the contrast sensitivity under mesopic
and photopic conditions but under the mesopic conditions the average
pupil size was 4.2.

It\'s pretty small. The range was 2 to 7 so if they can go back and look
at how well the people with 7 millimeter pupils functioned versus the
two, that might be useful information.

CHAIRPERSON WEISS: Just so we can summarize somewhat, in terms of the
issues about pupil, Dr. Matoba, you would prefer that the sponsor come
back and actually stratify the pupil size versus the results or the
contrast sensitivity to give some gauge if that had an impact?

DR. MATOBA: Or at a minimum patient satisfaction because, I mean, I
share Dr. Grimmett\'s concerns that 4.5 is a size that is of some
concern. There are some theoretical problems with that.

CHAIRPERSON WEISS: Okay. So you would like the sponsor to come back and
give the agency some information about pupil size and patient
satisfaction.

Dr. Grimmett, would you like to go beyond that as far as the pupil size
concerns or that would satisfy the issues?

DR. GRIMMETT: Well, I would prefer that a statement is made in the
labeling just stating that the lens optic size is 4.5 millimeters and
mesopic large pupil sizes may induce visual aberration. Something of
that nature just to state what we\'re all getting at. We know that to be
true both from our clinical practices and from literature.

I think the Table 10.7 that list almost a third of patients at moderate
or severe, any symptom at night is pointing to the fact that there are
some visual aberrations going on here even in this subset age 50 and
older.

My concern comes to knowing other things obviously about the market. The
FDA nor the manufacturers has a duty, nor is obligated to handle
off-label uses, but we know from the array of lens that in the market
place surgeons offer off-label uses of clear lens extraction for
presbyopia.

I think for this particular product with a 4.5 millimeter optic if that
PreLEX presbyopia lens exchange surgery was advocated, I think that we
need to preemptively put in the labeling alerting the physician to the
fact that this is a 4.5 millimeter lens otic and has some concerns
regarding dim illumination mydriasis. That\'s why I would favor putting
it in.

CHAIRPERSON WEISS: Specifically for that concern would you want to say,
\"This is the size of the optic. We don\'t know the effects if you are
younger and you have a large pupil and consequently this is not
recommended for PreLEX?\" Do you want to go that specific?

DR. GRIMMETT: No, I wouldn\'t say that. I think it is a 4.5 millimeter
optic. The manufacturer has already told us that this particular lens
sits however many millimeters back from the corneal plane making the
effective optical zone that the pupillary plane equals X.

They threw out a number of 5.4 but that was for a lens that sat further
posterior so do the calculation for wherever this lens happens to sit.

Given those two facts, then I would make the next statement, that pupil
sizes larger than this may induce visual aberrations, e.g., mydriasis
and dim illumination.

CHAIRPERSON WEISS: But then aren\'t we speculating just like we were for
the oblique lens?

DR. GRIMMETT: Arthur?

CHAIRPERSON WEISS: I take that as a yes.

DR. BRADLEY: Mike\'s deferring to me and presumably he knows I\'m good
at speculating. I think we don\'t need to speculate at all. I think
it\'s very simple optics. I mean, if you have a small enough optical
zone and the pupil size is large enough, light will get to the retina
without passing through the optics.

We are all aware, I think, right now that if a laser came to the panel
right now that was designed to correct small amounts of myopia or
intermediate levels of myopia with an optical zone considerably smaller
than the anticipated pupil size, we wouldn\'t approve such a device.

CHAIRPERSON WEISS: What\'s the statement you want to put in there? Cut
to the chase.

DR. BRADLEY: Cut to the chase.

CHAIRPERSON WEISS: Does anyone have a line that they would suggest to
sort of summarize the concerns expressed here?

Dr. Coleman.

DR. COLEMAN: Maybe you could put it under the precautions that data for
subjects younger than 50 years of age or with pupils greater than 4.5
millimeters unless this is provided to the FDA is not available and so
the effect in these individuals of the small optical zone is of concern
or is unknown.

DR. GRIMMETT: Mike Grimmett. I think Alice said the range actually was
something up to 7 millimeters, right? So there were some patients that
had larger pupil size in all fairness. It\'s just that it wasn\'t
stratified.

We are using \-- I think the basis here is we\'re not using evidence
from their study to say what happens in patients with large pupil sizes
with a 4.5 millimeter optic. We simply don\'t have those data.

CHAIRPERSON WEISS: I think we\'ll get back to what Dr. Matoba suggested
originally is this is a concern and if the sponsor gave this information
to the agency, then the agency could determine what to do with that
information as far as additional labeling. I see Dr. Rosenthal agreeing
so I think that is probably \--

DR. GRIMMETT: I think the FDA understands the intent of our concern
regarding dim illumination mydriasis.

CHAIRPERSON WEISS: What about the concern of Dr. McMahon\'s about the
increased uveitis and CME rate? Do panel members want to include that in
labeling and, if so, how?

Dr. Coleman.

DR. COLEMAN: I think that\'s in the labeling in terms of they gave the
rates of the uveitis and CME.

CHAIRPERSON WEISS: Do you want to say anything additional about it or
the table is fine?

DR. COLEMAN: There is something written. In addition, also so you know,
on the precautions on page 2 of 18 the immersion biometry is recommended
for axial length so that is there.

CHAIRPERSON WEISS: While you are looking that up \--

DR. McMAHON: Dr. Weiss, can I address that question?

CHAIRPERSON WEISS: Yes, Dr. McMahon.

DR. McMAHON: The purpose of raising those and, again, sort of trying to
adhere to the issue of limiting speculation was a relative concern of
whether we should address the age of the patient, therefore, the
exposure of the eye to this lens until greater information is made. The
data that they have is the data they have.

There is a trend but maybe that is just a statistical fluctuation. One
would expect in a moving object inside the eye a higher incidence of
these sorts of things. The reason I mention those two isn\'t to
specifically point them out in the labeling. They are already
identified. The issue is should we ask the sponsor to limit implantation
of this lens to an older age group until such time there is adequate
evidence to go to a younger age group.

CHAIRPERSON WEISS: Dr. Grimmett, do you have an opinion on that?

DR. GRIMMETT: I certainly would make a statement that the lens is only
studied in age 50 or older and that it is not recommended for less than
age 50 for the reasons we\'ve stated. Dr. McMahon\'s concern about
there\'s no data and the ongoing iritis or the CME issue. The issue that
we previously discussed regarding young patient mydriasis, I think that
is a second strong reason not to recommend under the age of 50.

CHAIRPERSON WEISS: You could have a blanket statement saying use of this
lens in younger patients with larger pupils. Or you can just say simply
that it hasn\'t been studied, just as we said, in anyone younger than
50.

DR. GRIMMETT: The lens was not studied in patients younger than 50 and
use of the lens in patients younger than 50 is not recommended. I would
even go further. Not to just say it wasn\'t studied. It\'s not
recommended from this panel. Is anyone here recommending that it is used
under age 50? Okay. It\'s not recommended.

CHAIRPERSON WEISS: I would differ with that. I would personally prefer
to say we don\'t know rather than whether we recommend it or not. We
don\'t have any data to recommend it or not. I think it would be unfair
to say we don\'t recommend it without any information.

DR. GRIMMETT: Well, when they come up with data the labeling will be
changed. The FDA is reasonable and they will look at new data for under
age 50 and if it supports safety and effectiveness under that age group,
then that statement will be removed.

CHAIRPERSON WEISS: How does everyone feel about this discussion?

Dr. Bradley.

DR. BRADLEY: I think Jayne\'s suggestion that we simply don\'t comment
on whether we think it\'s a bad idea to fit this with younger eyes I
think is wrong. Although we don\'t have any data, we have clear theory
which tells us that if the pupil is too large, light will get past the
optical zone and then you will have a tremendous amount of blurred light
on the retina.

It\'s not speculation in this particular case. It must be true. I think
putting a warning in there to alert the physician to this is reasonable.
I agree with Mike.

CHAIRPERSON WEISS: Do we have that data though? Isn\'t that what Dr.
Matoba is requesting to seek patient satisfaction with pupil size?

DR. BRADLEY: Suspicion is in this age group. You will find very few
patients who have pupil sizes the same size that we would expect
routinely in this 18 to 30 age group.

CHAIRPERSON WEISS: So should we be waiting for extra data before you
make that statement as opposed to making that statement without the
data? I\'m throwing this out.

Dr. Matoba.

DR. MATOBA: We don\'t know that. I think the average pupil size is small
but the range, for example, as I said for the contrast sensitivity for
the mesopic conditions the average pupil size was 4.2 but the range was
2 to 7 so there may be a number of patients that you can look at to
answer this question.

DR. BRADLEY: I think you have a couple of patients and that does not
allow you to answer the question. I mean, basically you need a large
sample here and you are only going to get a few people who have a pupil
size that large in this age group where it is routine. My students you
put them in a room and they all have pupils of 7 millimeters or more.

CHAIRPERSON WEISS: Dr. Coleman, do you have a comment on this?

DR. COLEMAN: I think we need the data so I agree with Dr. Matoba.

CHAIRPERSON WEISS: So actually I would sort of like to address this
point as well. It sounds like there is a little bit of a conflict. I
would like a show of hands in terms of panel members who would support
putting an item in there saying that specifically this is not
recommended for patients below a certain age.

The alternative for the other panel members who have a concern but
don\'t want to voice that opinion would be to get the additional data
and then make a conclusion on that basis. In any case, let\'s just state
it as I did initially.

Can you vote in the affirmative if you would like to put something in
here saying that this is specifically not recommended for younger
patients and we could determine whatever age you want to put. That\'s
affirmative by Dr. Grimmett, Dr. Young, Dr. McMahon, and Dr. Bradley.
How many of you would vote against that? We have affirmative by Dr.
Coleman, Dr. Ho, and Dr. Matoba, and Dr. Weiss who has no vote in this
process. We will move on from there.

MR. McCARLEY: Excuse me. I have a question.

CHAIRPERSON WEISS: Yes, Mr. McCarley.

MR. McCARLEY: Rick McCarley. Just a question to the FDA. Are there any
lenses, intraocular lenses for cataract surgery that are 4.5 right now
that are approved? Is there one? So, in fact, this is the first \--

DR. ROSENTHAL: Rosenthal. The answer is no.

MR. McCARLEY: Okay. So this, in fact, would be the first one. But just
for consistency sake, wouldn\'t this apply to labeling for all
intraocular lenses if you are saying an intraocular lens should never be
placed into a patient whose pupil size is larger than the optic? Why
would you restrict that to this lens? Why wouldn\'t you put that across
all lenses?

CHAIRPERSON WEISS: Dr. Bradley.

DR. BRADLEY: I think the point you make is a good one but we obviously
are just considering this lens. Other lenses have been dealt with
perhaps differently but we are dealing with this particular lens and we
have a concern about this lens.

It seems that the precedent, fortunately, is not there but there is a
4.5 optic zone out there already approved. If that were the case, then I
think we would be challenged doubly here. But the fact is that is not
the case. I think this is a new type of small optic zone that warrants
our careful consideration of this pupil size issue.

MR. McCARLEY: But it seems to set a precedent that you shouldn\'t have
any patient regardless of their age. I mean, this is an age cutoff issue
we are dealing with here. Age cutoff based upon pupil size, I\'m not
sure those are \--

CHAIRPERSON WEISS: We can try to make the labeling for each specific PMA
as excellent as we can make it and that\'s our goal. We actually had a
similar issue last meeting and I think we had a similar discussion last
meeting about having higher standards for one PMA than another. We would
like to have standards for every PMA so if that is what the panel wants
to do, that\'s what the panel wants to do.

Dr. Rosenthal, did you have a comment on that? No comment. Then Dr.
Matoba and then Dr. Ho.

DR. HO: Allen Ho. We have no evidence to recommend for or against this
lens based on that age. Therefore, I have no evidence, no basis to make
a statement.

CHAIRPERSON WEISS: Dr. Matoba.

DR. MATOBA: Plus the concern is regarding pupil size so what if you are
25 but you have a very small pupil and you can\'t get that IOL. That is
why I don\'t agree with recommendation to prohibit or not to recommend
patients who are under 50.

CHAIRPERSON WEISS: Dr. Bradley.

DR. BRADLEY: Yeah. I think Alice is correct but I think the warning
could be one not simply of saying we discourage the use of this lens for
people under age 50 but explain why. It\'s an issue of pupil size.
Clearly then if a patient comes along with a small eight-year-old size
pupil in a 20-year-old eye, then you could \--

CHAIRPERSON WEISS: Then to play devil\'s advocate, if you are concerned
about the age is not the age but the pupil size, why don\'t we just go
back to Dr. Matoba\'s initial suggestion to ask the sponsor to provide
the data of satisfaction correlating with the pupil size rather than
eliminating a 30-year-old with a 3 millimeter pupil.

Dr. Bradley.

DR. BRADLEY: For the reason I made, that it is unlikely that the data
exist because there are so \--

CHAIRPERSON WEISS: We can ask the sponsors here. We can ask the sponsor.
Sponsor, does this data exist?

DR. BRADLEY: So the question to the sponsor would be then how many
patients had 7 millimeter pupils. My guess is in this age group not
many.

CHAIRPERSON WEISS: Dr. Rosenthal.

DR. ROSENTHAL: Rosenthal. I just wondered if I could ask the panel what
if you had an 80-year-old eye with a 20-year-old pupil.

CHAIRPERSON WEISS: I\'m in total agreement with you. We should be
confining our comments to \-- if the age issue is solely dependent on
the pupil problem and not Dr. McMahon\'s concern about the lens moving
back and forth and perhaps causing CME and uveitis which is a separate
problem.

If your concern is solely based on the pupil, then you have to talk
about what you want to talk about which is the pupil. The sponsor will
let us know how many large pupils did you have in the study.

DR. GORDON: Pupil size measurements were made for the contrast to the
substudy. We will have to go back and look at that. We had some very
small pupils and pupils up to 7 millimeters. The stratification that we
performed in comparing the results both with and without the glare
source showed no differences in that controlled testing.

CHAIRPERSON WEISS: So specifically for glare we don\'t know the number
of large pupils and small pupils. I don\'t know if you can provide us
while you are here today or otherwise you will provide it to the agency
at a later date. Basically there was no correlation even if you had
small numbers. Is that correct?

DR. GORDON: There was no correlation. We\'re looking it up so we\'ll get
back to you.

CHAIRPERSON WEISS: Okay. That\'s fine. Thank you.

Are you satisfied, Dr. Bradley? Maybe that\'s an open question. Maybe I
shouldn\'t have asked that. Perhaps we should go on.

DR. BRADLEY: Next.

CHAIRPERSON WEISS: Dr. Grimmett.

DR. GRIMMETT: Dr. Grimmett. Dr. Matoba\'s point is well taken. I am most
interested in getting after mydriasis issues with this lens. That is
obviously the key issue to me and I think Dr. Bradley agrees with that.

Based on the comments of the sponsor, I don\'t think they have the data
Dr. Matoba is asking for. She is asking for patient satisfaction data
such as that nighttime difficulty stuff associated with stratification
of pupil sizes.

I just don\'t think that was done. I just strongly urge the panel to
have some type of statement regarding pupil size and the visual
aberrations we know that happens when light is passing through an
aphakic section of the entrance pupil.

CHAIRPERSON WEISS: If sponsor has any other comments on this issue, I
would appreciate it.

DR. GORDON: We\'ll have to come back to you. We\'ll come back to the FDA
with the exact numbers. I don\'t have the numbers on the distribution
but we do have that information.

CHAIRPERSON WEISS: Okay. Fine. So we have a bit of \-- I think everyone
is in agreement that we do want extra data from the sponsor as far as
patient satisfaction and how this relates to pupil size.

I think there is a small majority, at least there was five minutes ago,
for saying this is not recommended for younger patients. The folks who
voted, I guess that \-- the people who voted, did anyone change their
vote on the basis of this discussion or have all the votes stayed the
same? Dr. Bradley.

DR. BRADLEY: I think my vote stays exactly the same but I think the
discussion clarified the issue. The issue is not one of age. It\'s a
matter of pupil size so maybe it could be reworded to emphasize the
importance of pupil size.

CHAIRPERSON WEISS: So actually that is changing it because we were
specifically \-- this statement was specifically targeted at age, not
pupil size. I think you have changed your vote, in which case that
statement would come out.

Dr. Grimmett.

DR. GRIMMETT: Dr. Grimmett. I think there were two parts to the age
comment. Part A was that this lens has not been studied in patients
younger than 50. I think everyone will agree that is a statement of
fact.

Part B was this lens is not recommended for patients under age 50 so I
think the discussion now I would \-- for all the reasons cited you can
have a 20-year-old pupil and an 80-year-old patient as Dr. Rosenthal
pointed out.

I would agree that I am most interested in pointing out the dim
illumination mydriasis issue versus the lens optic rather than making an
age cutoff. I would vote take out Part B if we have the other issue
stated.

CHAIRPERSON WEISS: I have been told the agency gets it which I think is
a hint to me to move on.

I do want to just go through the labeling and clarify which of these
will be in the physician labeling, which will be in the patient
labeling, and which will be in both because there are two sets. Table
10.3, 10.5, and 10.7, would that be in both physician and patient
labeling?

DR. HO: Allen Ho. I do think that\'s valuable for the patient. If I may
add, for patient labeling I would like to make a suggestion. I think
Anne Coleman had suggested in Attachment 2, right-hand column, the
sentence, \"Almost all of the study patients could pass their driver\'s
test,\" etc., which I think is misleading because it\'s a very strong
statement.

But deleting that statement actually forces the patient to go to a table
and not all patients will go to a table. I think a way to soften that
would be to maintain the statement but delete almost all and start it
with study patients and put in percentages.

CHAIRPERSON WEISS: Actually, I think I had criticized that because it\'s
not that they can pass a driver\'s test now and they have the skill to
drive, it\'s that they have a visual acuity of a certain level that will
allow you to pass a driver\'s test.

DR. HO: In particular, the near vision test, the percentage of patients
that can do that without glasses, I think, is valuable adjunct to that
which is included in the table. My fear is that patients aren\'t going
to look at a table and I like it in the text.

CHAIRPERSON WEISS: Perhaps \-- okay. I\'m still going to go back because
I just want to finish the one item with the tables and then go on to a
separate issue which is a statement to the patients in terms of what
their functional visual acuity will be.

Table 10.3 is a bilateral patient survey wearing spectacles during
waking hours and to see at night. Table 10.5 is activities without
spectacles. Table 10.7 is difficulty with night activity. I think these
can be included in both patient and physician.

The comment that you were making, Dr. Ho, in terms of a summary
statement as far as what your functional visual acuity is, I think you
would like something a little bit more than this table. We do have
something down here indicating that for many near vision tasks many
patients still needed glasses. You would like something indicating that
the majority of patients had visual acuity at distance which was good
enough to drive without glasses.

DR. HO: No. I\'m speaking specifically to the patient labeling, the last
sentence of the first page. There was a recommendation to delete that
sentence. I think we can \-- I think it\'s valuable but I think it\'s
misleading.

My recommendation would be to delete \"almost all of the\" and start the
sentence with, \"Study patients could achieve driving vision\" instead
of \"pass driving test.\" In parentheses, \"Shop or apply their makeup
(X percent.)\" Or, \"Read newspaper without glasses or contact lenses (X
percent.) I think that is valuable information that is extracting it
from the table and putting it into text.

CHAIRPERSON WEISS: That sounds like a good suggestion to me. Any
thoughts on that? If not, then if we could include that as well. You
would like that specifically for the patient labeling just to change the
last sentence and put in statistics, percentages.

Another item was result may not be as good if only one eye is implanted
with the lens. Do we want that in physician labeling or in patient and
physician labeling? Both I hear from Glenda Such.

Dr. McMahon.

DR. McMAHON: Do we really want to say it that way? It is an issue that
we don\'t know what the results would be.

CHAIRPERSON WEISS: Actually it was about 18 percent difference in terms
of the uncorrected near and distance.

DR. McMAHON: Yeah, but that\'s a unilateral case versus unilateral \--
an aphakic situation versus a pseudophake with CrystaLens versus
pseudophake with another type of lens.

CHAIRPERSON WEISS: We could have two statements or what would you
propose? We could reflect the data. The question would be there is no
information about how you do if you only have one lens implanted and the
other eye is pseudophakic with a different lens.

DR. McMAHON: That would be my suggestion.

CHAIRPERSON WEISS: So break it up into two sentences? Patient and
physician, one or the other or both?

DR. McMAHON: I guess I would err on both.

DR. YOUNG: I would concur both.

CHAIRPERSON WEISS: Glenda Such and Terri Young both indicate they would
like that in patient and physician labeling. Dr. Coleman is still
scribing. Correct? That\'s why we call you the scribe. This has happened
to me once before so I have a learning curve.

The third item. The YAG at less than 12 weeks or the results of YAG
capsulotomy at less than 12 weeks is not known. Patient, physician, or
both?

Dr. Young.

DR. YOUNG: I would say both. I wanted to stress that I know that\'s in
the \-- it\'s already written here but it is to stress that the
accommodative performance isn\'t known.

The other issues that are listed as possible complications meaning lens
decentration or possible repositioning of the lens which we already know
to be true for YAG capsulotomies performed for posterior chamber
intraocular lenses and standards lenses. It is the accommodative
performance that we are not sure of.

CHAIRPERSON WEISS: The fact that immersion method gives you a better
success rate, that is already in physician\'s labeling?

DR. YOUNG: That is already in physician\'s labeling.

CHAIRPERSON WEISS: Do we want to put that in patient labeling? Fine. No
patient\'s labeling, just physician\'s labeling. We are going to remove
from the patient labeling the fact the lens moves backwards and
forwards. I don\'t know if that was in physician\'s labeling.

I guess we could say it is in physician\'s labeling so \-- yeah, it\'s
in patient\'s labeling but if it\'s in physician\'s labeling I would
presume the panel would want it removed from both. Am I correct on that?
I see some nods. That means yes.

We have a suggestion that this lens was not used in patients \-- this
lens was only used in patients above the age of 50 and the results in
patients younger are not known. Patient and physician labeling?

DR. HO: Yes.

CHAIRPERSON WEISS: I hear a yes from Glenda Such and some affirmatives
from Dr. Ho and Dr. Matoba.

Another suggestion, long-term stability of the hinge as well as the
accommodative refractive effect have not been determined. This is
physician labeling. Should it also be patient labeling?

MS. SUCH: Yes.

DR. HO: I hear from Glenda Such, our consumer representative, yes. I see
some affirmative nods.

DR. BRADLEY: Could you clarify the second part of that?

CHAIRPERSON WEISS: The second part was basically referring to question 2
of the agency that the stability of the hinge and the stability of the
accommodative refractor effect, the long-term stability of these have
not been either looked at or shown or demonstrated, whatever. That is
going to be in both.

The indication that for near vision many patients still required for
close visual tasks for near vision and however you want to wordsmith it,
many patients still will require glasses. Patient or physician or both?
Both.

The claim of accommodation of one diopter. Patient, physician, or both
that this lens is capable of accommodation of one diopter? Glenda.

MS. SUCH: I don\'t think it has to go on the patient.

DR. McMAHON: Neither.

CHAIRPERSON WEISS: Dr. McMahon agrees. That will just be physician
labeling.

DR. McMAHON: No, I said neither.

CHAIRPERSON WEISS: Oh, neither.

DR. HO: I would agree with that.

CHAIRPERSON WEISS: I think Glenda Such just felt that should not go in
patient labeling, I presume because the issue of one diopter and such
would require more explanation.

Dr. McMahon didn\'t feel that it should go in either. I will direct you
back to \-- that was actually question 1(a) of the agency. Any other
comments on this one?

Dr. Bradley and then Dr. Matoba.

DR. BRADLEY: I think that should be put in there. I think that the
evidence that we have currently seems to indicate that maybe about one
diopter of accommodation. I think that\'s what the physicians want to
know.

CHAIRPERSON WEISS: Dr. Matoba and then Dr. Grimmett.

DR. MATOBA: I agree with Dr. Bradley but I would like to ask Dr. McMahon
why he thinks it should not be in there.

DR. McMAHON: Because I\'m not fully convinced of accommodation.

CHAIRPERSON WEISS: You\'re consistent. This is good.

DR. McMAHON: I lost that vote before.

CHAIRPERSON WEISS: The fact that the only powers that were looked at
were 16.5 to 27.5, that will be physician\'s labeling. Should that be in
patient\'s labeling? No from Dr. Grimmett and no from Dr. Coleman. That
would be physician labeling. I assume that someone is going to propose
and Dr. Matoba has brought this up of getting the data about pupil size
and patient satisfaction and the issue of not being recommended for
patients less than 50 I think was removed. Is that correct? That was
removed.

Dr. Bradley.

DR. BRADLEY: There was a suggestion that it be replaced by a pupil size
issue.

CHAIRPERSON WEISS: Well, correct me if I\'m wrong. I believe that what
the decision was was to get data and then have the agency make the
recommendations on the basis of the data.

Dr. Bradley.

DR. BRADLEY: No. I think what happened was our original suggestion by
Dr. Grimmett was modified but the sentiment was still there that some
warning about the issue of people size should be included. Perhaps it\'s
worth taking another vote on that because that did get lost I think.

CHAIRPERSON WEISS: Perhaps you can give the statement that would make
you happy and then we can have a vote on it.

Dr. Grimmett.  It doesn\'t have to be exact.

DR. GRIMMETT: FDA can wordsmith it. I mean, just the sentiment that we
can vote on should there be a pupil size warning with a lens optic 4.5.
Do people agree with that if the FDA wordsmiths an appropriate
statement? Is anyone against that?

CHAIRPERSON WEISS: Does everyone \-- can we have a show of hands for
those of you who would like a warning statement for a pupil size
depending on what the data is like or not depending on the data? What if
the data shows that there is no correlation?

DR. GRIMMETT: Well, sure. I don\'t think there is any data but if the
data shows something, clearly go with the data. If there is no data,
then I think there should be a pupil size warning statement.

CHAIRPERSON WEISS: Okay. Dr. Bradley agrees with that. Let me rephrase
this. What the intent is is still to have the sponsor come to the agency
with data, any data they have, on large pupil sizes.

If that data does indeed show that pupil size was not at all related to
patient satisfaction so that the concern of some of the panel members
with a small size 4.5 optic is unfounded, then there would not be an
additional warning here. But if either the data obviously showed that
there was a problem or that the data was insufficient, then \--

Donna Lochner.

MS. LOCHNER: I just wanted to mention that we currently have a
requirement that lenses that are less than 5.5 millimeter, we require
sponsors to put a warning in their labeling that physicians should
consider the effects of pupil size. That discussion is wonderful.

CHAIRPERSON WEISS: So, in other words, that was going to go on there
anyway.

MS. LOCHNER: Right.

CHAIRPERSON WEISS: Okay. Rolling right along.

PARTICIPANT: Thank you, Ms. Lochner.

DR. HO: Were you holding out for a reason?

CHAIRPERSON WEISS: I think you like our company. Dr. Coleman or anyone
else, were there any other labeling issues?

Mr. McCarley.

MR. McCARLEY: From the dark side, I guess. Mr. McCarley with Ophtec and
the consumer rep. My question is this seems to be, and correct me if
I\'m wrong, FDA, please, this is the second cataract product that will
have patient labeling. The array multifocal that came before and then
this one. Is that correct?

DR. ROSENTHAL: Rosenthal. That\'s correct.

MR. McCARLEY: Okay. It seems to me that now the patient is choosing
which lens goes into the eye. I guess I understood the rationale behind
the array lens is because they were potential safety issues and this one
seems to be more on efficacy.

CHAIRPERSON WEISS: In this case the sponsor has given us this labeling
for the patient so we are not suggesting it to them.

DR. ROSENTHAL: This is Rosenthal. The sponsor gave it to us at our
suggestion.

CHAIRPERSON WEISS: Oh. Okay.

DR. ROSENTHAL: It was our experts in some other branch, some other
division, some other world that we work with, another office that really
felt that it should be there for the patient to be able to understand
the various issues related to this revolutionary concept.

MR. McCARLEY: Okay. And given that, should there be a comparative
analysis or comparative information in the patient labeling because you
don\'t have cataract surgery every day so the patient that opens it up
and they don\'t have anything to compare it to.

DR. ROSENTHAL: Absolutely not because the lens is not compared to all
the other ones.

MR. McCARLEY: Right. Well, my point is how does the patient understand
the one shot of the data rather than understanding what it\'s compared
to like a standard \--

DR. ROSENTHAL: The same way that every laser hands out patient labeling
regarding its laser. We don\'t do a consumer report on various devices.
We just make decisions on single devices and it was the recommendation
of our experts the patient labeling be provided.

CHAIRPERSON WEISS: I\'m going to ask Glenda Such, our consumer
representative, to make a comment.

MS. SUCH: I would probably have a comment on this one. Yes, as in any
product there is going to be things changing all the time so having
something in the labeling would be like really, really horrible to have
that has just the one product. You know that\'s going to change.

Sorry, but it will change. They are going to have to do like they do
with everything else. They are going to have to compare products. This
is part of how they are going to do it by being able to look up these
type of patient information pieces.

CHAIRPERSON WEISS: Are there any other issues concerning labeling? Does
the agency have any issues? Otherwise, we\'ll go on to the \--
otherwise, I believe we go on to the \--

DR. ROSENTHAL: Question 4. Rosenthal.

CHAIRPERSON WEISS: Yes, Dr. Rosenthal.

DR. ROSENTHAL: Question 4, I think.

CHAIRPERSON WEISS: Question 4. Excuse me.

4\. Do the data in PMA P030002 support the proposed indication
statement?

o Primary implantation for the visual correction of aphakia in adult
patients with cataracts.

o Provide improved near, intermediate, and distance vision without
spectacles.

Any comments on this or should we just put it to how many of the panel
members agree with this indication? Can you raise your hand if you
agree? So we have Dr. Coleman agreeing, Dr. Bradley agreeing, and Dr.
McMahon agreeing, and Dr. Ho and Dr. Matoba agreeing. And Dr. Grimmett
wants clarification.

DR. GRIMMETT: Dr. Grimmett. Dr. Bradley, didn\'t you make an earlier
point which I thought was valid that the lens provides without
spectacles improved intermediate and distance? Then you had a comment
that near wasn\'t up to snuff and you had a way of phrasing that.
Wouldn\'t that address the second half of the indication here?

CHAIRPERSON WEISS: Dr. Bradley.

DR. BRADLEY: Yeah. I think the point that I was making is that the
sponsor has given us good evidence, I believe, that this lens will
provide patients with well-focused, or I used the word, clear vision at
distance and at intermediate, but not at near. However, the quality of
vision at near is clearly superior to that provided by the standard
lens. That was their statement.

CHAIRPERSON WEISS: Dr. Bradley, though \--

DR. GRIMMETT: Should then that second part be modified or no?

DR. BRADLEY: Well, the crux of that statement and perhaps your query is
the issue of improved relative to what? Improved intermediate and
distance vision? Many of these patients obviously started off with a
cataract and many of them started off with a refractive error so, sure,
it\'s improved.

Improved near? Sure. Most of these patients started off with presbyopia
so it seems to be improved. It\'s one of those statements which if you
water down the statement enough, yeah, it\'s going to be true.

It depends on how people interpret it. The concern that I have that I
mentioned very early on was that the sponsor today stated in their
conclusion that this lens provided clear vision at these distances.

CHAIRPERSON WEISS: They are shaking their head. I think they \-- well,
perhaps I could have \-- you can come to the podium and answer that,
Judy.

DR. GORDON: Maybe I can clarify.

CHAIRPERSON WEISS: Yes.

DR. GORDON: The use of the word clear was a generic term at the end of
the presentation and much has been made of it that is not implied in the
indication, in the labeling, or anywhere in the PMA application.

CHAIRPERSON WEISS: Just for their blood pressure and just for the length
of the meeting, let\'s just take out the word clear. That is going to be
banished from this room for the next hour or two. Let\'s address
ourselves to the indications that they have written here which are
basically provide improved near, intermediate, and distance vision
without spectacles.

Dr. Matoba.

DR. MATOBA: Can we provide these up? Has everyone agreed that the first
is okay?

CHAIRPERSON WEISS: We can do whatever we want. Would you like to \-- why
don\'t we do that and let\'s break it up as Dr. Matoba has suggested
into the indication, \"Primary implantation for visual correction of
aphakia in adult patients with cataracts.\" Can we have a vote for those
panel members who would agree with that? So we have a unanimous vote on
the first portion of No. 4.

Dr. Matoba.

DR. MATOBA: If the patient is aphakic, I mean, has had a previous
cataract extraction with an intact capsule. Would dialogue not be
indicated in that patient?

DR. GRIMMETT: Dr. Grimmett. You might not be able to get it in the bag.

DR. MATOBA: It has to be captured.

DR. GRIMMETT: It has to be bag fixated according to their prior
statements.

DR. MATOBA: Adults patients, do you want to say anything about the age
at this point?

CHAIRPERSON WEISS: Dr. Rosenthal.

DR. ROSENTHAL: No, please. We have a standard way of describing it.

DR. MATOBA: Oh, okay. We only have to address ourself to these two
statements and if one of these statements is not agreed to by a majority
of the panel, then this could be crafted in a way that the panel members
would find it helpful or more honest or more representative of this PMA
but we don\'t have to add extra information.

The conditions will address those issues such as age and such. I think
the panel does agree with the first statement of primary implantation.
Now we\'ll address ourselves to the second statement. I would like to
have a vote for those panel members who agree with the second statement
that the indication here has been shown that this does provide improved
near, intermediate, and distance vision without spectacles.

Can we have those panel members that agree with that raising their
hands? We have Dr. Coleman, Dr. Ho, Dr. Bradley, Dr. Grimmett, Dr.
Young, and Dr. McMahon, and Dr. Matoba. I think that has just become
unanimous for reasons unclear why it wasn\'t before but, hey. Time I\'m
told.

I think then we have answered question No. 4 and I want to know if there
are any other additional issues the panel wants to raise or the agency
wants to raise. Otherwise, we will go on to the open public hearing.

Dr. Lepri, is that okay with you? Do you have anything else you would
like us to address?

DR. LEPRI: I have nothing else.

CHAIRPERSON WEISS: You have nothing else for us to address. Good. We\'re
going to go on to the open public hearing. Is there anyone who would
like to make a relevant comment? I\'m not sure why there was laughter
but I\'ll just move on from there.

Seeing no relevant comments, or any irrelevant ones either, we will now
go on to the FDA closing comments for five minutes. Does the FDA have
any closing comments they want to make?

DR. ROSENTHAL: Rosenthal. No, we do not.

CHAIRPERSON WEISS: Dr. Rosenthal, thank you.

Would the sponsor like to add any closing comments? Yes.

DR. GLASSER: Adrian Glasser. Ladies and gentlemen, members of the panel,
and the FDA. I would like to thank you, first of all, for your very
insightful review and comments on this presentation. I would like to
dwell a little further on accommodation. I am paraphrasing Dr.
Bradley\'s comments and I am sure Dr. Bradley will correct me if I\'m
wrong.

I believe that the data has presented a demonstration of one diopter of
actual accommodation or accommodative amplitude. I would ask you to
consider the rhetorical question of how much accommodation is required
in order to say that accommodation is present. After all, a small change
in focus for a eight-year-old child is a large change in focus for an
80-year-old cataract patient. I would like to talk also a little about
subjective and objective measurement of accommodation which I think is
highly relevant here. Subject measurement of accommodation requires that
the subject, the patient, report when blur is first perceive.

This is certainly influenced by many factors, some of which have been
discussed here today including depth of field, psychophysical factors
such as blur sensitivity and contrast sensitivity because the subject
must be able to identify when something is blurred.

It requires that the subject initiate the accommodative response. They
must perceive blur and they must respond to that blur by accommodating.
It also then, the subjective method, requires that the subject report on
the level of blur perceived to identify the accommodative amplitude.

So in subjective measurement of accommodation it requires cooperation
from the subject. It requires clear stimulus presentation. The subject
must see the stimulus clearly. It requires the subject to initiate the
accommodative response.

The object of measurement of accommodation, and here presented the ideal
case, would require no participation from the subject, would require no
self-initiated accommodative response, and would utilize a totally
objective accommodation measurement.

Drug-stimulated accommodation. We can ask the question how can
accommodation be stimulated and measured totally objectively?
Pharmacological stimulation of accommodation is an appropriate way of
inducing an accommodative response. It does not require that the subject
initiate the accommodative response. An objective techniques would then
ideally be used to measure the accommodative change.

I contend that this is perhaps the most appropriate way of objectively
demonstrating whether or not accommodation occurs. Dr. Paul Kaufman from
the Department of Ophthalmology at Madison University in a recent
editorial in the Blue Journal of Ophthalmology identified that the use
of 6 percent \-- and I paraphrase him here \-- identified that the use
of 6 percent pilocarpine is an objective method to stimulate
accommodation and cyclopentolate to cycloplegia accommodation, and then
to use an objective technique to measure the induced change.

This is exactly what was done in the study presented here today in 10
eyes of five patients in the substudy where an object of technique,
namely A-scan ultrasound, was used to measure the movement of the IOL.

The A-scan measurements of forward movement of the CrystaLens in nine
out of 10 eyes provides support for the claim that this lens moves
forward in the eye with the stimulation of accommodation.

The near acuity data measured through the distance correction show a
significantly greater proportion of CrystaLens implanted eyes with
functional near vision at all acuity levels as compared to a standard
IOL.

CrystaLens subject required a mean near add of 1.2 diopters less to
achieve best near visual acuity than the standard IOL subjects. The data
served to establish the functional accommodation provided by the
CrystaLens.

The patient survey data are a very important assessment of the
satisfaction of the patients and it identifies that 93.8 percent of the
CrystaLens patients performed most daily tasks without spectacle
correction.

Indeed, as many as 77.5 percent read most things without spectacles.
When asked how often they wear spectacles, 73.5 percent identify that
they never wear spectacles or wear them almost none of the time.

In summary, the objective measurements of change in anterior chamber
depth show forward movement of the lens. The near and intermediate
visual acuity measured through the distance correction provide evidence
of accommodation consistent with the proposed mechanism of action and
the objective measurements.

This is further corroborated by the fact that the CrystaLens subjects
required less add to achieve best corrected near acuity than subjects
implanted with standard intraocular lenses.

This is the first accommodating IOL to be presented for review by the
panel. I believe this is a unique opportunity for an exciting and
significant technological development. This may set the stage for future
significant developments in cataract surgery beyond simply restoring
distance acuity and near acuity.

Much work remains to be done to fully understand and characterize
pseudophake accommodation. There will no doubt be significant future
developments in this fast evolving field. However, we believe that the
data presented here offered the first real and compelling evidence in
support of the notion that accommodation can be restored after cataract
surgery with an accommodating intraocular lens.

We would like to thank the panel and the FDA for their interest and
assistance in bringing the CrystaLens to the panel for consideration.
Thank you very much.

CHAIRPERSON WEISS: I would just to thank the sponsor for their very
clear presentation and the panel members and the agency for also
elucidating this PMA for us.

We will be moving on now to voting options which Sally Thornton will now
read.

EXECUTIVE SECRETARY THORNTON: The medical device amendments to the
Federal Food, Drug, and Cosmetic Act is amended by the Safe Medical
Devices Act of 1990 allows the Food and Drug Administration to obtain a
recommendation from an expert advisory panel on designed medical device
premarket approval applications, or PMAs, that are filed with the
agency.

The PMA must stand on its own merits and your recommendation must be
supported by safety and effectiveness data in the application or by
applicable publicly available information. Safety is defined in the Act
as reasonable assurance based on valid scientific evidence that the
probable benefits to health under conditions on intended use outweigh
any probably risks.

Effectiveness is defined as reasonable assurance that in a significant
portion of the population the use of the device for its intended usages
and conditions of use when labeled will provide clinically significant
results. Your recommendation options for the vote are as follows:

First, approval if there are no conditions attached.

Second, approvable with conditions. The panel may recommend that the PMA
be found approvable subject to specified conditions such as physician or
patient education, labeling changes or a further analysis of existing
data. Prior to voting, all of the conditions should be discussed by the
panel.

Third, not approvable. The panel may recommend that the PMA is not
approvable if the data do not provide a reasonable assurance that the
device is safe or if a reasonable assurance has not been given that the
device is affective under the conditions of use prescribed, recommended,
or suggested in the proposed labeling.

Following the voting the chair will ask each panel member to present a
brief statement outlining the reasons for their vote.

Thank you, Jayne.

CHAIRPERSON WEISS: Thank you. At this time I would like to ask for a
motion to be made from the floor concerning this PMA from the panel.

Dr. Ho.

DR. HO: Approvable with conditions.

CHAIRPERSON WEISS: Can you state what you would like to be approvable
with conditions? The motion would be if you agree with No. 4, then this
is the indication.

DR. HO: That\'s correct.

CHAIRPERSON WEISS: Can you state that?

DR. HO: Well, why don\'t you read it?

EXECUTIVE SECRETARY THORNTON: No.

CHAIRPERSON WEISS: I can\'t state it for you so if you could just state
what is written down.

DR. HO: I would move to make PMA P030002 approvable with conditions to
support the proposed indication statement of primary implantation for
the visual correction of aphakia in adults patients with cataracts to
provide improved near, intermediate, and distance vision without
spectacles.

CHAIRPERSON WEISS: Is there a second of the motion?

DR. YOUNG: I second it.

CHAIRPERSON WEISS: Dr. Young seconds the motion. We would need to make a
motion now to introduce each separate condition. That motion will then
be seconded and voted on as they come up.

Dr. Coleman, can you introduce some of these conditions?

DR. COLEMAN: Some of them. I would recommend as a condition that we
include tables 10.3, 10.5, and 10.7 in both the patient and physician
labeling and making sure that we include percentages in the patient
labeling in the last sentences on one of attachment 2.

CHAIRPERSON WEISS: Do we have a second of that?

DR. GRIMMETT: I second.

CHAIRPERSON WEISS: We have a second of that motion. I would like to then
put this to a vote. All of the panel members who would like to vote in
the affirmative, please raise their hand. This is just for \-- we are
going to go through each of the conditions and then at the end we go
through the PMA. This is for this particular condition. Dr. Grimmett,
Dr. Young, Dr. McMahon, Dr. Bradley, Dr. Matoba, Dr. Ho, and Dr. Coleman
have all voted yes.

Any other conditions, Dr. Coleman?

DR. COLEMAN: Second condition is that in patient physician labeling
information on the effectiveness of YAG capsulotomy prior to 12 weeks
has not been established to be included.

CHAIRPERSON WEISS: Can you restate that, please?

DR. COLEMAN: That information on the effectiveness of YAG capsulotomy
prior to 12 weeks has not been established.

CHAIRPERSON WEISS: I believe that Dr. Young had put that condition
forward and I think, and you can correct me if I\'m wrong, is that her
concern was the accommodative performance after YAG capsulotomy that was
performed at less than 12 weeks has not been established. Is that
correct?

DR. YOUNG: That is correct.

DR. COLEMAN: We can amend mine that the effectiveness of accommodative
ability after YAG capsulotomy prior to 12 weeks has not been
established.

CHAIRPERSON WEISS: Does anyone second that?

DR. YOUNG: I second it.

CHAIRPERSON WEISS: Dr. Young seconds it. We will have a vote on that.
All members who would like to vote in the affirmative, please raise your
hand. All of those who would like to vote against, please raise your
hand. All those who would like to abstain, please raise their hand. So
Dr. Grimmett, Dr. Young, Dr. Bradley, Dr. Matoba, Dr. Ho, Dr. Coleman
all vote in the affirmative and Dr. McMahon abstains.

DR. COLEMAN: The next condition is to not include in the patient label
any information about the immersion biometry but to include it as it is
in the physician labeling.

CHAIRPERSON WEISS: Perhaps we don\'t even need that as a condition
because it\'s already in the physician labeling.

DR. COLEMAN: The next condition is to remove the movement of the lens
from the patient labeling.

CHAIRPERSON WEISS: Anyone second that condition?

DR. McMAHON: Second.

CHAIRPERSON WEISS: Dr. McMahon seconds. We will have a vote. All those
who would like to vote in the affirmative, please raise your hand. This
is unanimous. Dr. Coleman, Dr. Ho, Dr. Matoba, Dr. Bradley, Dr. McMahon,
Dr. Young, and Dr. Grimmett.

DR. COLEMAN: Next condition is to mention that the visual results are
not know if the CrystaLens is placed in one eye and the other eye is
pseudophakic with another standard IOL in both patient and physician
labeling.

CHAIRPERSON WEISS: Anyone second?

DR. McMAHON: Second.

CHAIRPERSON WEISS: Dr. McMahon seconds. Can we have a vote? All those
who would like to agree, please raise your hand. It\'s unanimous.

DR. COLEMAN: The next condition is to include in both physician and
patient labeling that information on subjects less than 50 years of age
available or has not been studied.

CHAIRPERSON WEISS: Perhaps \--

DR. COLEMAN: Subjects less than 50 years of age have not been studied
with the CrystaLens as of this time.

CHAIRPERSON WEISS: Second?

DR. HO: Second.

CHAIRPERSON WEISS: Dr. Ho seconds. Can we have a vote? All those who
would like to vote in the affirmative, raise your hand. This is
unanimous. We can move on.

DR. COLEMAN: Include in both the patient and physician labeling that the
long-term stability of the lens has not been established for the hinge
or the accommodative refractive effect.

CHAIRPERSON WEISS: Second? Dr. Bradley seconds. Can all those who agree
please raise your hand. This is unanimous as well.

DR. COLEMAN: Include in both physician and patient labeling that
patients will require or may require glasses after the use of their
CrystaLens for near, intermediate, or distance acuity.

CHAIRPERSON WEISS: Would you like to sort of reflect that this is more
likely a problem at near than at distance or intermediate?

DR. COLEMAN: Yes. Patients may require glasses at near distance or
intermediate acuity. However, it is more likely to be seen at near
acuity.

DR. BRADLEY: We can work on the wording of that.

DR. COLEMAN: Yeah, the wordsmithing.

DR. HO: Spectacle requirement may be higher with near.

CHAIRPERSON WEISS: I\'m told by Sally that the FDA basically understands
what the panel is trying to reflect so we don\'t have to wordsmith it. I
think the concern is more near than at distance.

DR. COLEMAN: And that it would be in both the physician and patient
labeling.

CHAIRPERSON WEISS: So with that sentiment, we are going to be voting on
sentiment as opposed to words, could we have everyone who agrees please
raise their hand? Unanimous. Maybe I should go for sentimental vote.
It\'s quicker.

Okay. Yes?

DR. COLEMAN: Mention that there is approximately one diopter of
accommodative ability in the physician label or accommodative amplitude
of one diopter in the physician label.

CHAIRPERSON WEISS: Any seconds? Dr. Bradley seconds. A vote, please.
Raise your hand if you agree. So we have Dr. Grimmett, Dr. Coleman, Dr.
Matoba, and Dr. Bradley vote yes. All those who disagree? Dr. McMahon
and Dr. Young and Dr. Ho vote no. Was there an abstention? No
abstention.

EXECUTIVE SECRETARY THORNTON: Four to three.

CHAIRPERSON WEISS: Four to three. That would be passing. Any other?

DR. COLEMAN: Yes. To mention as a precaution that the range of axial
lengths is 21 to 26.6 millimeters and the lens powers used in the study
were 16.5 to 27.5 diopters.

CHAIRPERSON WEISS: And if you \--

DR. COLEMAN: In the physician labeling.

CHAIRPERSON WEISS: Any second?

DR. HO: I second it.

CHAIRPERSON WEISS: Multiple seconds including Dr. Ho. Can we have a
vote? All those agree raise your hand, please. This is unanimous. Next.

DR. COLEMAN: To mention on page 2 that atrophy sulfate 1 percent should
be given immediately postoperating and postoperative day No. 1.

CHAIRPERSON WEISS: Physician or patient?

DR. COLEMAN: Physician labeling.

CHAIRPERSON WEISS: Do we have a second?

DR. YOUNG: Second.

CHAIRPERSON WEISS: Dr. Young seconds. Can we have a vote? All those
agree, please raise your hand. This is unanimous.

DR. COLEMAN: To give a precaution that the effective vitrectomy on the
performance of the lens is unknown in physician labeling.

DR. McMAHON: Second.

CHAIRPERSON WEISS: Seconded. Everyone who agrees, raise your hand. It is
unanimous.

DR. COLEMAN: To also include under adverse events in the physician\'s
labeling the possible increased risk of CME associated with sulcus-bag
placement of the haptics.

CHAIRPERSON WEISS: A second do we have?

DR. HO: Second.

CHAIRPERSON WEISS: Dr. Ho seconds. All those who agree, please raise
your hand. Dr. Young, Dr. McMahon, Dr. Coleman, Dr. Ho, Dr. Matoba, Dr.
Bradley agree. All those who disagree raise your hand.

DR. GRIMMETT: Abstain.

CHAIRPERSON WEISS: And all those who abstain. We were getting to you,
Mike. Those who abstain, Dr. Grimmett abstains.

DR. COLEMAN: To include in the physician\'s label the information on
stability of near, intermediate, and distance acuity looking at less
than or minus half a diopter change of MSRE over a year.

CHAIRPERSON WEISS: I\'m not clear what that condition is.

DR. COLEMAN: That was to include those tables on the stability of the
near distance and intermediate acuity where they could see how the
dioptric changes in terms of percentages of those that had less than a
half diopter from forms three to four and then four to five.

CHAIRPERSON WEISS: Dr. Grimmett, we haven\'t seconded it so I think we
can discuss it.

DR. GRIMMETT: Sponsor agreed to that in their response to your concerns
when you stated it in your \--

DR. COLEMAN: Right. We don\'t have to vote on it then?

CHAIRPERSON WEISS: Well, if they agree, the we\'re not altering what
they want to do so we don\'t have to add that.

DR. COLEMAN: Okay. To mention in the physician\'s and patient\'s
labeling that pupil size is important in terms of \--

CHAIRPERSON WEISS: I think we don\'t have to mention that because that
is part of the agency\'s protocol anyway. I would \-- there is one thing
that I think that we should discuss \--

DR. COLEMAN: The study. Sorry, this is my last one. That the sponsor
will get back to the FDA with information about pupil size and
stratification on pupil size and the satisfaction surveys.

CHAIRPERSON WEISS: Fine. Do I have a second for that?

DR. GRIMMETT: Yes.

CHAIRPERSON WEISS: Dr. Grimmett seconds. Can I have a vote? Everyone
votes in the affirmative, please raise your hand. That\'s unanimous. The
only other one that I have here that I can see is that the visual acuity
may not be as good if you have your phakic in one eye and you only have
the CrystaLens placed in the other eye. I think that was a table that we
talked about including.

DR. COLEMAN: To include the information that subjects that had the
primary implant were about 80 percent uncorrected near acuity. Those
that had bilateral implantation around 97 percent.

CHAIRPERSON WEISS: Do we have a second for that? Dr. Matoba seconds. Can
we have a vote? Everyone who agrees, please raise your hand. This is
unanimous. Are there any other conditions, Dr. Coleman, or any of the
other panel members?

We will now have a final vote. Would all in favor of the main motion
with its condition signify by raising their hand? The PMA passes
unanimously. That is, this PMA is approvable with conditions.

I will now poll each of the individual panel members to ask them to give
us the reasons why they voted affirmative.

Dr. Coleman.

DR. COLEMAN: I believe that there is reasonable assurance of safety and
effectiveness of the CrystaLens.

CHAIRPERSON WEISS: Thank you.

Dr. Ho.

DR. HO: I would first like to thank the sponsors for presenting a clear
dataset and a concise presentation. I thought they did an excellent job.

I do think that this is a safe and I\'m excited about the prospects of
evaluating patients who have this in. I do think it can be, in their
words, revolutionary and efficacious.

I have a little trouble with the issue of accommodation. That may be my
lack of understanding of the issue, although I think it\'s a very
complicated subject. I think there is a suggestion that their may be an
accommodative effect but I think an N of 5 to 10, that\'s underwhelming
and not substantial enough for me to include accommodating in the
language. Otherwise, I do think this is approvable with our conditions
specified.

CHAIRPERSON WEISS: Dr. Matoba.

DR. MATOBA: Alice Matoba. I felt that from the patient\'s point of view
there was adequate evidence of efficacy and safety.

CHAIRPERSON WEISS: Dr. Bradley.

DR. BRADLEY: I think is an exciting new product. I was disappointed with
the quality of the data but I think it is demonstrated efficacy,
although somewhat marginally so. That\'s what I voted to approve.

CHAIRPERSON WEISS: Dr. McMahon.

DR. McMAHON: First of all, even though I\'ve been rather tough all day
on this accommodation business, I do want to acknowledge and thank the
sponsor for a generally well done presentation both of the sponsors
themselves, the consultants, and the investigations. It\'s always much
easier when there is a well-organized study when we have to read these
volumes and volumes of document. I certainly appreciate the organization
of the study.

I vote for approval with conditions from the point if view that I still
have some concerns about this business about true measurement of
accommodation under nonpharmacologic circumstances. I do not buy the
argument that Paul Kaufman\'s suggestion is the best way to do that. I
would flatly disagree with that.

I think it would be in the sponsor\'s best interest for all of us to
actually have that answer what this really does accommodate, if there
really is true accommodation or not.

I think the lens is safe. I still have a little bit of anxiety with
regard to a lens moving in the eye over a period of decades as to what
that\'s going to do. The data at this point is supportive of it.

The visual acuity information I think is quite impressive. That is the
principle reason that I voted for it.

CHAIRPERSON WEISS: Dr. Young.

DR. YOUNG: I also concur that there is a reasonable assurance of safety
and efficacy. The issues of accommodation are murky. As a pediatric
ophthalmologist I see this as a prototype, if you will, as good
potential for pediatric patients with amblyopia. I applaud the sponsors
for their excellent presentation.

CHAIRPERSON WEISS: Dr. Grimmett.

DR. GRIMMETT: Dr. Grimmett. I would also like to thank the sponsor for a
thorough and clear presentation. I voted approval of the conditions
because the application showed me reasonable assurance of safety and
effectiveness. Thanks again.

CHAIRPERSON WEISS: We are going to have any comments from Glenda Such
and Mr. McCarley.

MS. SUCH: Glenda Such here. As consumer representative I don\'t vote but
I would concur and I would have voted in favor if I could have. I think
that the study was well put together and I think the comments that were
made and the issues that were addressed were ones that I myself would
have had. I think a job well done was done today.

CHAIRPERSON WEISS: Mr. McCarley.

MR. McCARLEY: This is Rick McCarley. I don\'t have anything else to add.

CHAIRPERSON WEISS: Well, thank you. I think PMA PO30002 has been dealt
with. I would like to thank the sponsor for an excellent presentation
and as well the agency and the panel.

Before we conclude, Sally Thornton may have some remarks.

EXECUTIVE SECRETARY THORNTON: I just wanted to thank the panel for their
review of this document and the time they spent here and abroad
reviewing it.

I also wanted to make the announcement that we have canceled the July
panel meeting so that should be up on the web shortly but I wanted you
all to know today. Thank you very much and have a very safe holiday.

(Whereupon, at 3:02 p.m. the meeting was adjourned.)