FOOD AND DRUG ADMINISTRATION

 

CENTER FOR DEVICES AND RADIOLOGICAL HEALTH

 

OPHTHALMIC DEVICES PANEL

 

107^TH MEETING

 

THURSDAY,

FEBRUARY 5, 2004

 

      The Panel met at 9:00 a.m. in Salons B-D of the Gaithersburg Marriott Washingtonian Center, 9751 Washingtonian Boulevard, Gaithersburg, Maryland, Jayne S. Weiss, M.D., Chair, presiding.

 

PRESENT:

JAYNE S. WEISS, M.D., Chair

ARTHUR BRADLEY, Ph.D., Voting Member

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

MICHAEL R. GRIMMETT, M.D., Voting Member

WILLIAM D. MATHERS, M.D., Voting Member

TIMOTHY T. McMAHON, O.D., F.A.A.O., Voting Member

KAREN BANDEEN-ROCHE, Ph.D., Consultant

RICHARD CASEY, M.D., Consultant

ANDREW J. HUANG, M.D., M.P.H., Consultant

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

OLIVER D. SCHEIN, M.D., M.P.H., Consultant

JANINE A. SMITH, M.D., Consultant

WOODFORD S. VAN METER, M.D., Consultant

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

ANDREW K. BALO, Acting Industry Representative

SARA M. THORNTON, Executive Secretary

 

FDA REPRESENTATIVES:

EVERETTE T. BEERS, Ph.D.

GERRY W. GRAY, Ph.D.

BERNARD P. LEPRI,, O.D., M.S., M.Ed.

DONNA R. LOCHNER

JEFFREY TOY, Ph.D.

A. RALPH ROSENTHAL, M.D.

 

 

 

SPONSOR REPRESENTATIVES:

RICK McCARLEY

STAN BENTOW, Ph.D.

R. DOYLE STULTING, M.D., Ph.D

VANCE THOMPSON, M.D.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

                    A-G-E-N-D-A

 

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

 

Sara M. Thornton, Executive Secretary

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

      Conflict of Interest Statement............ 8

      Appointment to Temporary Voting Status... 11

 

OPEN PUBLIC HEARING............................ 12

 

OPEN COMMITTEE SESSION, Jayne S. Weiss, M.D., Chair

 

DIVISION UPDATE

 

A. Ralph Rosenthal, M.D., Director............. 40

 

BRANCH UPDATES

 

Donna R. Lochner, Chief, Intraocular and Corneal Implants Branch   41

 

Everette T. Beers, Ph.D., Chief, Diagnostic and Surgical Devices Branch 42

 

PMA P030028

 

SPONSOR PRESENTATION

 

ARTISAN Myopia Phakic Intraocular Lens......... 44

 

Panel Questions for the Sponsor................ 77

 

FDA PRESENTATION

 

Jeffrey Toy, Ph.D., Team Leader............... 108

Bernard Lepri, O.D., M.S., M.Ed, Clinical

Reviewer...................................... 109

Gerry W. Gray, Ph.D., Statistician............ 116

 

LUNCH

 

 

 

COMMITTEE DELIBERATIONS

 

Panel Questions for FDA....................... 151

 

Primary Panel Reviews:

 

Dr. William D. Mathers........................ 158

Dr. Oliver D. Schein.......................... 168

Dr. Marian S. Macsai-Kaplan................... 179

 

PANEL DISCUSSION OF PMA P030028

to include FDA questions to the Panel......... 189

 

30-MINUTE OPEN PUBLIC HEARING SESSION......... 303

 

FDA - CLOSING COMMENTS

 

SPONSOR - CLOSING COMMENTS.................... 307

 

Voting Options Read........................... 310

 

PANEL RECOMMENDATION TAKEN BY VOTE............ 316

 

POLLING OF PANEL VOTES........................ 344

 

COMMENTS FROM CONSUMER AND INDUSTRY

REPRESENTATIVES............................... 350

 

FINAL PANEL COMMENTS.......................... 352

 

OPEN MEETING ADJOURNED

 

 

 

 

 

 

 

 

 

 

 

 

 

               P-R-O-C-E-E-D-I-N-G-S

                                         9:01 a.m.

            DR. WEISS:  I'm going to ask everyone to take their seat, please.  We'll be starting shortly.  I would like to call this meeting of the Ophthalmic Devices Panel to order and note that there is a quorum present.  We will have introductory remarks by Sally Thornton.

            MS. THORNTON:  Good morning.  Permit me to introduce myself.  I'm Sara Thornton, Executive Secretary for the panel.  On behalf of the FDA I would like to welcome you to the 107th meeting of the Ophthalmic Devices Panel.

            Before we proceed with today's agenda, I have a few short announcements to make.  First of all, I would like to remind everyone to please sign in on the attendance sheet on the registration area just outside the meeting room here.  All public handouts for today's meeting are available at the registration table. 

            Messages for panel members and FDA participants, information, or special needs should be directed through Ms. AnnMarie Williams who is available at the registration area.  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, please, outside the meeting area.  Note the flyers on the door.

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

            Now, at this time I would like to announce the voting member appointment of Dr. William Mathers of the Casey Eye Institute in Portland, Oregon.  Dr. Mathers has been appointed to serve until October 31st of 2007.

            I would like to welcome our Acting Industry Representative, Mr. Andrew Balo, Vice President for Regulatory and Clinical Affairs with DEXCOM, Inc. in San Diego, California.  Mr. Balo also serves as the Industry Representative on the Neurological Devices Panel.  Mr. Balo is sitting in for our panel Industry Representative Mr. Ronald McCarley who has recused himself from today's panel deliberations.

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

            MS. SUCH:  Glenda Such, Lighthouse International, Consumer Representative.

            MR. BALO:  Andy Balo, Industry Representative.

            DR. SCHEIN:  Oliver Schein, Wilmer Eye Institute, Johns Hopkins.

            DR. BANDEEN-ROCHE:  Karen Bandeen-Roche, Department of Biostatistics, Johns Hopkins.

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

            DR. BRADLEY:  Arthur Bradley, School of Optometry, Indiana University.

            DR. MACSAI:  Marian Macsai, Evanston Northwestern Healthcare, Northwestern University.

            DR. GRIMMETT:  Michael Grimmett, the Bascom Palmer Eye Institute, the University of Miami.

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

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

            DR. CASEY:  Richard Casey, Charles Drew University, Jules Stein Eye Institute, Los Angeles.

            DR. COLEMAN:  Anne Coleman, Jules Stein Eye Institute, UCLA.

            DR. VAN METER:  Woody Van Meter, the University of Kentucky in Lexington.

            DR. HUANG:  Andrew Huang, University of Minnesota.

            DR. ROSENTHAL:  Ralph Rosenthal, Division of Ophthalmic and ENT Devices, FDA.

            MS. THORNTON:  I'd like to just announce that Dr. Janine Smith who will be in attendance at the panel will be here in a very short time.

            I'd like to now read the conflict of interest statement for the meeting on February 5, 2004.  The following announcement addresses conflict of interest issues associated with this meeting and is made part of the record to preclude even the appearance of an impropriety.

            To determine if any conflict existed, the Agency reviewed the submitted 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 matter that could affect their or their employer's financial interest.

            The Agency has determined, however, that the participation of certain members and consultants, the need for whose services outweighs the potential conflict of interest involved, is in the best interest of the government.  Therefore, waivers have been granted for Drs. Michael Grimmett, Oliver Schein, and Woodford Van Meter for their interest in firms that could potentially be affected by the panel's recommendations.

            Dr. Grimmett's waiver involves an imputed interest, a grant to his institution for the sponsor study in which he has no involvement and is uncompensated.  Dr. Oliver Schein's waiver involves two consulting arrangements, one pending for a competitor's unrelated device for which he has not received any compensation, and the second with a competitor's unrelated device for which he receives an annual fee between $10,000 and $50,000.  Dr. Van Meter's waiver involves an imputed interest, a stockholding in the parent of a competing technology firm in which the value is greater than $100,000.

            The waivers allow these individuals to participate fully in today's deliberations.  Copies of these waivers may be obtained from the Agency's Freedom of Information Office, Room 12A15 of the Parklawn Building.  We would like to note for the record that the Agency took into consideration other matters regarding Drs. Anne Coleman, Arthur Bradley, Michael Grimmett, Andrew Huang, Marian Macsai, Oliver Schein, and Jayne Weiss.

            Each of these panelists reported past or current interest involving firms at issue but in matters that are not related to today's agenda.  The Agency has determined, therefore, that the panelists may participate fully in all discussions.

            In the event that the discussions involve any other products or firms not already on the agenda for which an FDA participant has a financial interest, the participant should excuse him or herself from such involvement and the exclusion will be noted for the record.

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

            I would like to now 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 individuals as voting members of the Ophthalmic Devices Panel for this meeting on February 5/6, 2004.

            Karen Bandeen-Roche, Ph.D., Richard Casey, M.D., Marian S. Macsai-Kaplan, M.D., Oliver Schein, M.D., Andrew Huang, M.D., Janine Smith, M.D., Woodward Van Meter, M.D.

            For the record, these individuals are special government employees and consultants to this panel or other panels under the Medical Devices Advisory Committee.  They have undergone the customary conflict of interest review and have reviewed the material to be considered at this meeting.  Signed, David W. Feigal, Jr., M.D., MPH, Director, Center for Devices and Radiological Health.  Dated January 20, 2004.

            Thank you, Dr. Weiss.

            DR. WEISS:  Thank you, Sally.

            We will now open the open public hearing.  I will read a statement which was requested by the FDA. 

            "Both the Food and Drug Administration and the public believe in a transparent process for information gathering and decision making.  To ensure such transparency of the open public hearing session of the Advisory Committee, FDA believes that it is important to understand the context of an individual's presentation. 

            For this reason, the FDA encourages you, the open public hearing speaker, at the beginning of your written or oral statement to advise the committee of any financial relationship that you may have with the sponsor, its product and, if known, its direct competitors.

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

            I would call Glenn Hagele to the podium as the first public speaker.  You have up to 10 minutes.

            MR. HAGELE:  I need some assistance with the video.  Dr. Weiss, with your permission, could I come after the following speaker?

            DR. WEISS:  Why don't you stay up there if they can arrange that, Mr. Hagele, because we have a written letter from someone and perhaps we can use this window of time to read the letter while you're preparing your --

            MR. HAGELE:  Thank you.

            DR. WEISS:  If that would be agreeable.

            Sally Thornton has a letter that was sent in from someone who wanted to participate in the open public hearing but was not able to appear.

            MS. THORNTON:  This is a letter from Peter D. Van Patten, M.D., the Duluth Clinic Virginia in Virginia, Minnesota. 

            "Dear Ms. Thornton.  I had planned to make a short presentation at today's meeting but could not attend due to a scheduling conflict.  If possible I would like to have my following comments read into the record during the appropriate time slot of the meeting.

            My name is Peter D. Van Patten.  I have practiced ophthalmology since 1991.  I am also a subject in the U.S. clinical study of the ARTISAN Myopia Lens and have bilateral ARTISAN implants.  I have no financial interest in the ARTISAN lens or Ophtec, the sponsor of this study. 

            The purpose of my testimony is to provide additional information to the FDA and the FDA panel for consideration during today's discussions.  Prior to receiving ARTISAN lenses my refractions were -10.0 X -0.75 in both eyes.  Previously I was having increasing problems with contact lens wear to the point where the symptoms became intolerable. 

            After considering all available options, I decided to proceed with the ARTISAN lens implant.  My left eye received the ARTISAN lens in February '99, five years ago, and my right eye received the lens in March 2001, nearly three years ago. 

            My current refractions are -0.75 X -0.5 in the left eye and plano X -0.5 in the right eye.  I have an uncorrected acuity of 20/30 in the left eye correctable to 20/20 and 20/20 uncorrected vision in the right eye correctable to 20/15.  My outcomes were very successful and my overall vision is excellent. 

            I typically wear glasses only for night driving.  I have experienced mild night glare on occasion postoperatively that was not present prior to receiving the lenses.  However, I would rate the level of glare as minimal. 

            I have had significant functional improvements during my high visual demand activities such as ophthalmic surgery.  Also, I would rate my daytime vision as suburb.  I consider both procedures to be a success.  Over the past five years I have continued to discuss the ARTISAN lens as an important investigational surgical option with my patients whom I found to be appropriate candidates for open ARTISAN lens clinical trials.

            Based on my experience as a subject in this study, it is my opinion that the ARTISAN lens is a safe and effective lens when implants by a skilled surgeon.  I would ask that you consider my comments during your discussions and hope that you are able to make a favorable recommendation today so as to make this technology available to others who seek correction for high myopia.  Sincerely, Peter D. Van Patten, M.D."

            DR. WEISS:  Thank you, Sally.

            Mr. Hagele, are you ready?

            MR. HAGELE:  We are coming up momentarily.

            DR. WEISS:  Sounds good.  If you're still having difficulty, I understand that Ms. Woodlock does not have slides so she perhaps could do her presentation while you are getting that ready.

            MR. HAGELE:  Thank you.

            DR. WEISS:  Ms. Woodlock.  Would you mind, perhaps, giving your presentation from the table instead?  Thank you.

            MS. WOODLOCK:  I am Leslie Woodlock, Patient Advocate of the Surgical Eyes Foundation. We are a nonprofit organization whose constituency is consumers with sub‑optimal outcomes from refractive surgery. Our goals are simply to raise awareness of the risks of elective eye surgery, provide support and identify solutions for patients living with complications, and advocate for informed decision making. I personally became involved with the Surgical Eyes Foundation after failed LASIK surgery in 2000.

            I am here today to discuss the safety of phakic lOLs. While much of SEF's concern with the ICL was discussed at this panel's meeting on October 3, 2003, we would like the panel to address the following issues:

            Diameter selection is critical for centration of this device since under sizing could result in a failure of the lens to vault the anterior capsule properly, resulting in contact of the device with the capsule and subsequent anterior cortical cataract development.

            The need for a tight fit is recognized by the applicant and yet selection of the ICL diameter is to be based on the white‑to‑white measurement. Since no exacting correlation between the white‑to‑white measurement and the ciliary sulcus diameter exists, how will patients be protected from secondary cataract development?

            The increasing thickness of the physiologic lens with aging as well as during accommodation means that the desired post‑operative vault of the ICL will fluctuate and actually diminish over time. This has the potential to accelerate the development of anterior cortical cataracts.

            The incidence of endothelial cell loss is a repeated concern throughout the previous discussion. In the event that the ICL must be removed following a noted progression of anterior capsular opacities, there is no evidence suggesting that explantation of the ICL will be less harmful to the endothelium than its continued presence.

            Further, in cases of either device‑induced or naturally occurring cataracts, the ICL will have to be explanted before the implantation of a pseudophakic IOL. Clearly, for all patients, a second and possibly third intraocular procedure must be entertained with further potential for loss of endothelial cells.

            Continuing with our concern for loss of a functional endothelium, the dynamics of a shallow anterior chamber depth and progressive endothelial cell loss is unknown at this time. Most cases of Fuchs' endothelial dystrophy do not become clinically evident until patients are approaching their fifth decade. Will implantation of the ICL result in an even earlier loss of endothelial integrity and, ultimately, penetrating keratoplasty?

            These patients would appear to be at even higher risk for endothelial cell loss regardless of an allowable standard for minimal anterior chamber depth of 2.8 or 3 mm. It is not possible to assess risk for younger individuals at the time the ICL is implanted since they will not have visible indications for the condition.

            Revisiting the effects of aging of the physiologic lens, another consequence is the shallowing of anterior chamber. The applicant has found a correlation of shallow anterior chamber depth to endothelial cell loss. It is reasonable to suspect that aging of the crystalline lens and subsequent reduction of the anterior chamber depth will put older patients at increased risk for decompensation of their corneas secondary to endothelial dystrophy.

            In regard to implantation of this device, typically the risk of cystoid macular edema increases with each intraocular surgical procedure. In the case of device‑induced cataracts with subsequent explantation followed by implantation of a pseudophakic IOL, the potential for CME would be significantly greater.

            Correct positioning of the ICL requires a tight sulcus to sulcus fit with anterior displacement of the iris. The fact that the potential narrowing of the anterior chamber angles following implantation was not consistently examined via gonioscopy in the PMA suggests only a cursory concern with the potential for narrow angle glaucoma. Patients with naturally narrow anterior chamber angles as well as those whose angles will narrow subsequent to aging, are at higher risk for development of glaucoma.

            The presence of the ICL vaulting above the anterior capsule changes the dynamic of the posterior iris and its contact with the anterior capsule. The potential for pigment dispersion is very real as the ICL haptics rub against the posterior iris.

            Pigment dispersion has a known occurrence in the general population but does not manifest until the fifth decade. Implantation of this device in younger patients with a predilection for pigment dispersion will quite conceivably accelerate the process and lead to pigmentary glaucoma.

            Anterior cortical cataracts, narrow angle glaucoma, pigmentary glaucoma and endothelial dystrophy are naturally occurring conditions but are potential complications of the ICL. A very real possibility exists that health insurers will not cover the cost of treatment for these conditions since they could be viewed as secondary to an elective procedure.

            SEF is already aware of patients receiving corneal transplants following corneal refractive surgery who were denied reimbursement by their health insurer for this very reason. The negative impact on the patient is two fold. Either they will be denied coverage for a naturally occurring medical condition or they will have to pay for the deniable complications secondary to an elective surgery.

            The optical diameter of the ICL is listed as 4.65 to 5.5 mm. While the diameter of a posterior chamber ICL cannot be compared to the typical, stated ablation diameters of LASIK and PRK, it is interesting that the optical diameter is so small. Pseudophakic lOLs are typically in the 6.0 mm range and there are still patients who will notice glare and halos under low light conditions.

            Using our knowledge of pseudophakics' experience as a guide and, given that the population having ICL surgery would typically be much younger with larger pupils, it would seem very certain that many individuals will experience unwanted glare and haloes from spherical aberrations created by the uncorrected rays of light passing through the peripheral physiologic lens.

            Continuing on with the discussion of the optical diameter effects, it is necessary to mention the recent publication of Dr. Steven C. Schallhorn's study suggesting the irrelevance of pupil size to visual quality under mesopic and scotopic light conditions, in particular, that pupil size does not correlate with night driving performance.

            This oft touted study, however, does nothing to explain why numerous journal articles by leading refractive surgeons suggest the use of brimonidine tartrate (Alphagan), an adrenergic agonist that suppresses pupil dilation to produce a relative miosis, as well the direct‑acting miotic, pilocarpine, be used post‑operatively to suppress the ill‑effects of night time driving in refractive surgery patients.         The Surgical Eyes Foundation bulletin board is overflowing with empirical evidence from our patients and our participating doctors of the effectiveness of pupil constricting agents in the reduction of low light glare and halos. Our bulletin board already has one ICL patient complaining of this very thing and two well‑known refractive surgeons recommended Alphagan as the remedy.

            With regard to quality of vision, we ask that PMAs for all forms of vision correction devices be stratified by pupil size. The PDA should mandate that quality of vision be measured objectively with wavefront and other objective tests that have been utilized by optical scientists like Dr. Raymond Applegate that stratify results by pupil size, and that these results be published and made readily available to consumers with regard to any form of vision correction device.

            We have had many patients of all ages with large pupils post on our bulletin board about nighttime visual aberrations, regardless of refractive error. We understand that an effective optical zone on the corneal surface and the optic diameter of a lens that sits behind the iris are not comparable; however, we feel very strongly that patients with large pupils are at risk with this device.

            One common experience of patients visiting our web site and bulletin board is in regards to the informed consent agreement. While explanations of potential visual and physiological complications are discussed, patients typically do not understand the chronic and irreversible nature of those complications.

            Informed consent continues to be a major concern of SEF for elective refractive surgery. Unnatural visual effects seem to impact deeply on many patients sense of well being. The psychological emotional aspects of vision complications are not something potential patients can understand or be prepared to accept following negative outcomes.

            This completes my presentation.  On behalf of the board of trustees of the Surgical Eyes Foundation and our constituency, I wish to thank the Advisory Panel for the opportunity to express our concerns.  Thank you very much.

            DR. WEISS:  Thank you very much.

            And you will be limited to 10 minutes for your presentation.

            MR. HAGELE:  That should be more than adequate.  Good morning and thank you for the opportunity to address this panel. My name is Glenn Hagele. I am the Executive Director and founder of the Council for Refractive Surgery Quality Assurance, which from this point forward I will refer to by its acronym CRSQA.

            In the way of disclaimer, I have no financial interest in AMO or the ARTISAN phakic intraocular lens. My travel here today is self‑funded. Although I am the Executive Director of CRSQA, the opinions I express are my own and do not necessarily represent the opinions of individuals affiliated with CRSQA.

            CRSQA is a nonprofit consumer/patient organization that through its sister websites USAeyes.org and ComplicatedEyes.org receives over 800,000 visitors annually. We provide objective information about refractive surgery issues and resources for those unfortunate few who have encountered a poor refractive surgery outcome.       Additionally, CRSQA evaluates and certifies refractive surgeons based upon patient outcomes.

In addition to research of published studies and case reports, my interaction with patients provides me with a unique accumulation of anecdotal information and a perspective of a patient. The issues and concerns I will raise today all relate to communication between physician and patient.

            Potential refractive surgery patients, especially high myopes and high hyperopes, seek options. With a greater understanding of the advantages and limitations of corneal‑based refractive surgery, those with high refractive errors find the probability of achieving the convenience of a reduction of the need for corrective lenses less than spectacular.

            The phakic intraocular lens has been available outside the United States for the better part of a decade, and it is reassuring that this panel will have the opportunity to determine if a new option will be available to Americans.

            Not surprisingly, I have some concerns. I will leave to others to debate clinical data, and raise only those issue that from a patient perspective are of equal importance.

            Pupil Size.  Capt. Steven Schallhorn, MD of the United States Navy recently presented a significant performance‑based task study of 105 consecutive LASIK subjects to determine what effect preoperative scotopic pupil size has on postoperative night vision.

            Dr. Schallhorn's, and subsequent studies, found no direct correlation between scotopic pupil size and reaction‑based visual task performance. Although Dr. Schallhorn's study may

provide evidence that pupil size alone is a poor predictor of induced night vision problems, I have never heard Dr. Schallhorn say pupil size is not important.

            Pupil size may be a poor predictor of night vision problems, but as any doctor who has prescribed pilocarpine or Alphagan can attest, pupil size is the moderator of night vision problems, when they exist. Although these are two very separate issues, I ask that this panel be mindful of their interrelation.

            Furthermore, the corneal‑based LASIK procedure is not an intraocular lens. Even further, it is not a phakic intraocular lens. Decades of intraocular lens development have shown the importance of edge design and pupil size in regard to halos, starbursts, and glare in low illumination environments. It seems unreasonable to disregard this body of knowledge, regardless of the conclusions of Dr. Schallhorn's findings.

            Should this panel ultimately decide to approve the device presented today, I respectfully ask the panel to consider including in the labeling for both physician and patient that the probability of induced night vision problems when the scotopic pupil is larger than the size of the full optical correction of the device is not easily determined.

            I respectfully ask that the patient labeling include a representation of these effects and explanation of probable limitations on the patient, including difficulty driving at night and reading in low illumination environments.

            Learning Curve.  Today you will have the advantage of evaluating the safety and efficacy of the proposed device when care is provided by what can only be described as some of the best surgeons in the world. I submit that if this device is approved, it will be utilized by doctors who are, shall we say, of somewhat lesser distinction.

            With reports of as much as 20% incidence of anterior sub‑capsular opacities with the first few patients of other intraocular lenses when implanted by novice surgeons, it appears self evident that proper implantation of an phakic intraocular lens requires not only training, but practical experience.

            I have no reason to doubt that the Sponsor will provide significant training in this regard, and I have equally no doubt that this panel will insist on adequate training and proctoring. I believe, however, it is in the best interest of the patient to be informed of the experience of the prospective surgeon.

            Our organization provides a list of 50 Tough Questions For Your Doctor for patients to use as a guide in selecting a refractive surgeon. In our 50 Tough Questions we recommend that a patient seek a doctor who has performed at least 100 refractive procedures of the exact type intend to use on the patient, with the same equipment, and the same refractive error, and significantly more practical experience with similar surgical techniques.

            While this panel may find our recommendation of 100 a bit conservative and even restrictive, it does seem reasonable to assume the patient would like to know if he or she is the doctor's first unsupervised phakic intraocular lens patient.

            I respectfully request that this panel include in the patient labeling a statement indicating that training and practical experience of the surgeon may be an important factor in the probability of a desirable outcome.

            Induced Intraocular Pressure.  This panel is much better qualified to determine the safety of the Sponsor's phakic intraocular lens than I, but it appears reasonable to assume that the patient will require periodic evaluation of intraocular pressure during use of the phakic intraocular lens. Who will pay for this care?

            Phakic intraocular lens for the convenience of a reduced need for corrective lenses is an elective, arguably cosmetic, procedure. The patient who is making the decision to proceed is making this decision partly based upon cost.

            If significantly elevated long‑term care were required to maintain good ocular health after phakic intraocular lens implantation, the probable costs for examinations, visual fields, and medication to manage a surgery‑induced chronic condition would most probably be an important factor in the patient's decision to elect to have surgery in the first place.

            I doubt that it is within the power of this panel to require a doctor to provide long‑term cost estimates preoperatively, but it does seem reasonable that the patient labeling include an indication of the type and frequency of reasonably probable surgery related long‑term care.

            I'm sure that when presented with this probable treatment plan, the patient will not need the labeling to recognize that these costs should be a part of the decision regarding the relative value of a reduced need for corrective lenses.

            Endothelium.  There seems to be a lack of clear consensus on the long‑term effects of phakic intraocular lens on the quantity and quality of endothelium cells. In the clinical trials, a mandatory evaluation regime underlies the importance of this consideration. The Sponsor is requesting approval for implantation in patients as young as their twenties.         Assuming that the phakic intraocular lens would be utilized until natural cataract development when a person is in his or her sixties, the functional life of a phakic intraocular lens may be as much as 40 years. During this time, the need for regular evaluation of endothelial cell loss seems obvious.       Again, who is going to pay for these costs?

Like long‑term care for induced intraocular pressure, it seems reasonable that the patient labeling include some indication of the type and frequency of reasonably probable surgery related long‑term care.

            Summary.  The issues I raise all relate directly to the communication between doctor and patient. All suggestions are for the purpose of promoting that communication.  If properly informed of the immediate and long‑term issues relating to the Sponsor's phakic intraocular lens, I believe that those patients who elect to have phakic intraocular lens implants will have reasonable expectations and will be able to make the decision that best

meets their needs and desires.

            Lastly, I do hope that during the course of discussions today I will not hear the term "implantable contact lens". If this is a contact lens, then I've been wearing explantable phakic intraocular

lenses when I water ski.  Thank you very much for your time.

            DR. WEISS:  Thank you.  I have been told that there is someone in the audience who wanted to also participate in the open public hearing.

            DR. JOHN:  Yes.

            DR. WEISS:  Okay.  You have, well, Dr. Grimmett said eight minutes but actually it's now down to seven.  If you could identify yourself and any potential conflict.

            DR. JOHN:  Yes, ma'am.  Hi.  I'm Maurice John.  I'm an ophthalmologist from Louisville, Kentucky/Jeffersonville, Indiana, all in the same metropolitan area.  I'm medical monitor for Ophtec.  I am not paid by them at all except they paid for my plane fare and my hotel today.

            I have no stock which is very good news for Ophtec in that I don't have stock in their company.  They would be in trouble.  I implanted intraocular lenses starting in 1975.  I did radial keratotomy in 1980.  In 1993 I had a laser in Sao Paolo, Brazil and we believe the first LASIK was performed with my laser by a colleague of mine in 1993.  In 1995 I started doing LASIK in Sao Paolo to get ready for the United States.

            In October of 97 I was fortunate enough to implant the first five ARTISAN lenses in the United States.  Prior to that I had gone to Brazil and that summer of '97 implanted a couple of lenses down there.  Now I've done 200 plus ARTISAN lenses, the majority of which have been myopic and about 10 percent hyperopic.

            Starting out in October '97 I found out that there certainly is a learning curve to implanting this lens which has already been mentioned.  It is a short but steep learning curve and there is an advantage to being a good surgeon. 

            Mr. Hagele's excellent presentation mentioned that he encourages his patients to ask for a surgeon who has done 100 or more cases and that's going to be very, very difficult with an ARTISAN lens because there just aren't many of those people out on the planet.  I have a large, busy, refractive surgery practice and I don't know what that number should be but I've been doing it six years and, like I say, I've just done 200 plus of those.

            This lens needs space to be put in the eye, there's no doubt about that, but there is adequate technology to make those measurements to determine if there is adequate space.  I would also like to comment on glare.  Having done radial keratotomy since 1980 I can assure you that all those patients had starburst and glare and that did not kill radial keratotomy.

            Then I've done between five and 10 patients who are in the subset of people who have larger than 6 mm pupils and none of them have glare.  I strongly think the reason for that, especially in this population of people who are between -10 and -20 primarily they've had glare, super glare, all their life.  So if they get glare from this, it's pretty much peanut glare and then if it's a killer, then this lens can be removed really quite easily.

            After that point the problems are primarily if you estimate the anterior chamber depth they are surgeon related and we've seen that time and time again.  I introduced this lens in Brazil, as I said, in October of 1997 to my friend Eduardo Martinez who we think is the first guy to do LASIK in North or South America.  He was using other phakic IOLs and has switched to this and now gives paper presentations on it.

            I have been to South Africa many times.  I go to a meeting over there every two years and I introduced it in 1998 to some of my colleagues there.  They also had access to all the phakic IOLs that are available throughout the world. 

            My colleague, Jan Venter, is up in England now and he is working for a consortium and he gets referred all of the anterior segment surgeries that these LASIK boutiques find.  In September of last year he implanted 100 of these lenses.  That's how much he believes in their efficacy.

            The nice thing about this lens, having done a lot of refractive surgery, when I'm in the office and seeing patients, I walk by and I pull the chart off, I look at it and I see it's an ARTISAN patient  and I am so happy because I know that I'm going to be in and out of there quickly and that these patients are going to see well and we have not beat up their cornea trying to do -10.0 or 12.0 diopters on them.

            If they see 20/30 they are far happier than a 20/25 LASIK patient.  It's amazing.  My LASIK patients are always whining.  They have some slippage, especially the -7.0, -8.0, -9.0, -10.0 and they are always wanting enhancements even though they are 20/25.  These ARTISAN patients have tremendous quality of vision. 

            It's amazing to me.  I just keep reminding myself you're taking the very worse people on the plant, the one or two percent, bottom or top percent, depending on how you want to look at it, and basically pretty much nailing them, knocking a homerun every time up to the plate.

            My feeling is that patients should run to this lens and I've had some patients who you say FDA study and you've got to wait three months between eyes and they've gone elsewhere.  I've seen a couple of them come back and they said, "I should have listened.  I should have come."

            The problem we have is, and I had this in 1996, people wanted tried and true RK.  They didn't want LASIK.  We had the same thing here where 98 percent of these people's friends had LASIK, you know, quick, fast, next day, the American way, and this is a bit of a journey.  There are some people who have not had it and it's so unfortunate.  I think this lens is wonderful and thank you very much.  I hope I beat my seven minutes.

            DR. WEISS:  By 60 seconds.  Thank you.

            We will now close the open public hearing and we are going to move on to the open committee session starting with the division update.  Dr. Rosenthal.

            DR. ROSENTHAL:  Thank you, Dr. Weiss.  First, let me say that I very much appreciate Donna Lochner coming today because she is theoretically no longer with our division.  She has taken a det