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									 "White Paper on Sculpting"          page 1
September 15, 1989

 THE EVOLUTION AND PROSPECTS FOR LASER REFRACTIVE KERATOPLASTY



                         IRVING J. ARONS



                       ARTHUR D. LITTLE



I. Overview



The American public spends more than $16 billion annually for

vision care.   More than 60 million eye examinations are given

annually and nearly 60 million pairs of eyeglasses and 3 to 4

million pairs of contact lenses are dispensed.   In addition,

more than 1 million surgical procedures are performed to

correct vision deficiencies or for therapeutic reasons.



The laser has and continues to play an important role in the

treatment of eye disease.   Soon after the laser's discovery,

ophthalmologists were putting this unique tool to use in
stopping retinal bleeding and repairing retinal tears.    Today,

more than 90% of all ophthalmologists own or have access to a

laser for performing a myriad of treatments including retinal

photocoagulation, retinal reattachment, punching holes through

the trabecular network to alleviate glaucomas, clearing

vitreous strands and membranes, treating senile macular

degeneration, and clearing clouded posterior capsules or
"secondary cataracts".   Procedures under investigation include
 "White Paper on Sculpting"         page 2
September 15, 1989

photophacoemulsification (softening or fragmenting the lens

prior to cataract surgery), thermal sclerotomy, and treatment

of ocular cancers either through tumor vaporization or use of

photo dynamic therapy (PDT), among others.



One of the most important new procedures, if it can be shown to

be safe and efficacious, will be the use of a laser to reshape

the front surface of the eye, or as I have coined the term,

"corneal sculpting". (The more formal designations are laser

refractive keratoplasty or laser refractive keratectomy, or LRK

for short, and photorefractive keratectomy or PRK.)



The surgical potential of the use of ultraviolet radiation was

first reported by scientists in both the health sciences field

(Taboada and colleagues) and in the materials and electronics

industries (Rhodes; Ruderman; and Srinivasan).   Dr. Rahgaswamy

"Srini" Srinivasan of IBM's Watson Research Center reported in

1982 and 1983 that the excimer laser could make precise cuts in
organic plastic materials for use in the electronics industry,

or in human tissue such as hair.   Subsequently, two researchers

began to exploit the use of excimer lasers in the field of

ophthalmology.   Dr. Stephen Trokel, an ophthalmologist at

Columbia-

Presbytarian Medical Center in New York, heard about

Srinivasan's experiments and arranged to observe the procedure.
This led to Dr. Trokel's first experiments in Dr. Srinivasan's
   "White Paper on Sculpting"                             page 3
  September 15, 1989

  laboratories on bovine eyes in 1983.                       The work was originally

  done in the hopes of using the laser to make more precise cuts

  in the cornea in a radial keratotomy-type procedure, then

  coming into vogue for correcting myopia.                         At about the same

  time, an associate of Dr. Trokel's, Dr. Francis L'Esperance, a

  pioneer in the use of lasers in ophthalmology, saw a wider

  application for the excimer laser to ablate the front surface

  of the cornea, "corneal sculpting", and began efforts to

  develop both the technology and the medical research to exploit

  it1.     Today, at least three companies in the United States, and

  several more in Europe and Japan are funding research in an

  attempt to commercialize this procedure.                         Almost all of the

  work is being done with the argon fluoride (ArF) excimer laser,

  operating at 193nm, since experiments have shown that this

  wavelength appears to provide the "cleanest" cuts in corneal

  tissue, removing cellular matter by breaking molecular bonds

  one cell at a time, in a cold ablation or photodecomposition

  process without damaging adjacent tissue.                          The 193nm wavelength
  also appears to have non-mutagenic effects on corneal tissue.


   1
    At this time, 9 U.S. patents on methods and apparatus for accomplishing corneal sculpting
have been issued to Dr. L'Esperance and assigned to Taunton Technologies. Dr. Trokel claims to
be the original inventor of the concept and through his affiliated company, Visx, has filed an
interference action with the U.S. Patent Office. In addition, a patent has issued to Dr. Srinivasan
and his co-workers at IBM, covering the use of ultrviolet energy below 200nm to selectively
remove organic biological material.

So, to say the least, a confusing picture of ownership of technology exists that will most likely be
resolved by the courts, unless a mutually satisfactory agreement can be reached between the
involved parties.
 "White Paper on Sculpting"         page 4
September 15, 1989

In the procedure, which is being performed under FDA

investigational device exemption (IDE) protocols, a corneal

surface scan or refractive data is fed into a computer and the

computer program determines how much corneal stroma material

must be removed (usually only about 10 to 15% of the corneal

thickness in selected sectors) to form a contact lens-like

reshaping of the corneal contour.   The laser procedure takes

about 30 seconds, with the total procedure taking about 30

minutes.   The epithelium, or top surface layer of the cornea,

regenerates in about 48 hours.   Thus, the eye must be bandaged

for one or two days before the healing is completed.    Using the

procedure, or modifications of it, nearsightedness,

farsightedness and astigmatism can all be corrected, replacing

the need for eyeglasses or contact lenses for the majority of

people who elect the procedure once it becomes generally

available.   The problems seen to date are involved with the

healing of the cornea.   In some animal studies and early

clinical trials, several of the corneas treated have become
cloudy (hazy) and taken months to clear.   It is felt that this

is a matter of technique.   With shallower, smoother cuts, less

haze has been seen in later patients.   With improved

techniques, and perhaps in combination with the newly developed

epithelial growth factors that speed corneal healing, it is

believed that it is only a matter of time before this problem

is resolved.   A second early complication has been regression,
or thickening of the epithelium during regrowth.   Again, with
 "White Paper on Sculpting"         page 5
September 15, 1989

smoother, shallower ablations, the amount of regression or

corneal epithelium thickening is appreciably reduced.



In an earlier study done in March 1986 for Dr. L'Esperance's

group, your author forecast that within five years after

commercial introduction (following FDA marketing approval), a

minimum of 800 systems would be sold annually in the U.S., more

than 2000 would be in use, and 4 to 5 million procedures

performed annually.   Thus, we forecast that the successful

introduction of this procedure could have a marked impact on

the increased use of lasers in ophthalmology.    This forecast

was based on very preliminary information, before any of the

three companies now involved had built their laser systems.



In our latest study, completed in August 1989, after more

careful consideration of the clinical work now underway and the

attitudes of the ophthalmic community, we believe that fewer

systems will be sold annually in the U.S., because of slower
adoption by the medical community, and that closer to 2 million

sculpting procedures will be performed annually after about

five years following FDA marketing approval.    However, we

remain confident that the successful introduction of this

revolutionary technology into ophthalmic practices will change

the way vision is corrected forever.   Further, the new

technique will eventually change the way ophthalmologists
practice and result in an increase in dispensing of glasses and
   "White Paper on Sculpting"                           page 6
  September 15, 1989

  contact lenses by the remainder of the optical professions, as

  ophthalmologists find it more lucrative to become involved in

  laser refractive surgery than in simple refractions and the

  dispensing of eyewear.



  II. Other Medical Applications of the Excimer Laser



  The major application for the excimer laser in ophthalmology is

  for refractive correction, including the correction of myopia,

  hyperopia and low to moderate degrees of astigmatism.                              The

  latter is being approached in two ways; with the use of "T"

  cuts, similar to the way RK correction of astigmatism was done,

  and with the use of selected area ablation.                         The former

  technique has been successfully demonstrated both by U.S.

  clinicians and in West Germany by Theo Seiler, using the Summit

  Technology ExciMed UV200 laser.                   The latter technique, using

  area ablation to correct astigmatism, is under clinical

  investigation with the Taunton Technologies LV2000 laser. (And
  we believe this technique could also be incorporated into the

  Visx Twenty/Twenty Excimer Laser system.)2



  Besides the "cosmetic" refractive corrections, several

  therapeutic applications are under clinical study.                            Superficial


   2
    For more information about the U.S. and foreign companies involved in the development of
both excimer and other laser technologies for corneal sculpting, see the section following on The
Participants.
 "White Paper on Sculpting"          page 7
September 15, 1989

keratectomy or excimer laser smoothing of the cornea is being

investigated by all three of the companies noted above.     In

some cases, the use of a viscous liquid, methylcellulose, is

used to fill in the irregularities, and then the filled in

surface is smoothed without duplicating the irregularities

originally present.   The laser is also used to remove calcium

deposits, known as band keratopathies, and for the removal of

wedge-shaped growths known as pterygiums.     Corneal scars are

also being removed with the restoration of normal sight to some

patients in the clinical studies.



One company, Summit Technology, is investigating the use of

their laser for treatment of glaucoma through the formation of

a partial window or filtration bleb, in a process known as

partial excimer trabeculectomy.    Apparently, the process is

self limiting, as the escaping fluids prevents further tissue

penetration.


In addition to the ophthalmic applications noted above, the

excimer laser is under investigation in several other medical

specialties.   Probably the largest potential is in laser

angioplasty, or the clearing of peripheral and coronary

arteries obstructed with plaque.    Summit Technology, as well as

at least seven other companies, is experimenting with excimer

lasers, and is among the more than two dozen companies seeking
a laser solution to the clearance of clogged arteries.
 "White Paper on Sculpting"         page 8
September 15, 1989



Other potential medical applications for excimer laser

technology include arthroscopy and dentistry.   In arthroscopy

the laser may be used for the removal of both tissue and bone

fragments in endoscopic procedures, while in dentistry, the

laser may be used in penetrating enamel for access to caries

(dental decay), which can then be removed with a pulsed YAG

laser in "painless/drilless dentistry".



III. The Participants



In the United States, there are three companies currently

developing excimer laser systems for use in corneal sculpting,

and at least two others experimenting with competing

technologies.   In Europe and Japan, another three or four

companies are developing excimers and perhaps working on other

technologies as well.


U.S. Companies Involved in Excimer Laser Development



    Summit Technology -- Watertown, MA



    Summit has developed and built a compact ophthalmic excimer

    laser system, the ExciMed UV200, that is under study in

    both the U.S. and in Europe.   The unit has a built-in
    operating microscope and computer for controlling the
   "White Paper on Sculpting"                           page 9
  September 15, 1989

        sculpting and therapeutic procedures.                      Its lasers are also

        sold in Japan through a distribution agreement with Canon

        Sales.



        The company presently has four IDEs for clinical trials in

        ophthalmology and at least one for clinical investigation

        in coronary artery disease.                 The four ophthalmic IDEs

        include: 1) Superficial Keratectomy; 2) Photorefractive

        Keratectomy; 3) Partial Excimer Trabeculectomy for

        Glaucoma; and, 4) T-Excisions for Astigmatism.



        Some of the principal investigators3 include:



               John Hunkler - Kansas City, KS

               Robert Fenzyl - Garden Grove, CA

               Theo Seiler - Berlin, West Germany

               John Marshall - London, United Kingdom

               Roger Steinert - Boston, MA
               George Waring - Atlanta, GA




        Taunton Technologies -- Monroe, CT



        Taunton has developed a sophisticated, integrated,

   3
    According to the company, clinical trials are underway at 16 sites in the U.S. and Europe.
For further information contact the company directly.
 "White Paper on Sculpting"         page 10
September 15, 1989

    diagnostic/

    therapeutic advanced technology excimer laser system, the

    LV2000, that incorporates a digital keratoscope and Zeiss

    operating microscope into the laser system.    Colored

    displays of the dioptric power of the cornea guide the

    surgeon in computing the changes to be made.   Taunton holds

    IDEs for both refractive corrections, including correction

    of both myopia and hyperopia and removal of superficial

    scars, and for selected area ablation correction of

    astigmatism.   Taunton has an agreement with Alcon

    Laboratories to handle worldwide marketing to the

    ophthalmic community.



    Principle investigators include:



        Jim Rowsy - Oklahoma City, OK

        Richard Lindstrom - Minneapolis, MN


    Visx -- Sunnyvale, CA



    Visx has taken over the former CooperVision excimer laser

    program.   This system is perhaps the largest of the three

    and incorporates a high resolution observation/alignment

    operating microscope and video display, along with a mobile

    computer-controlled workstation for guiding the operator
    through the procedure and storing the patient data.      A
 "White Paper on Sculpting"         page 11
September 15, 1989

    modified version of an autorefractor can be used for both

    pre-op and post-op patient diagnostics.   The company holds

    at least two IDEs for both refractive and therapeutic

    corrections.



    Principle investigators include:



        Herb Kaufman and Marguerite McDonald - New Orleans, LA

        Walter Stark - Baltimore, MD



Non-Excimer Laser U.S. Companies



    Phoenix Laser Systems -- San Francisco, CA



    Phoenix is a newly public company (August 10, 1989)

    developing a pulsed doubled YAG, which they claim operates

    in a photodisruptive (plasma) mode to selectively remove

    corneal tissue.   As far as is known, no IDEs have yet been
    obtained to begin clinical trials.




    Intelligent Surgical Lasers -- San Diego, CA
 "White Paper on Sculpting"         page 12
September 15, 1989

    This private company is developing a fast pulsed, variable

    wavelength, solid state laser system for working on the

    eye.   According to their issued patent, the laser is a

    diode-pumped Er:YAG or Ho:YAG that can produce multiple

    wavelengths from a dispersion line device for spreading the

    wavelengths in each pulse.   The laser can also contain a

    frequency doubler to split the beam into components of

    different wavelengths.



Excimer Laser Development Work Underway Outside the U.S.



    Aesculap-Meditec (West Germany) has reported on masked

    excisions for making RK-type cuts and for making corneal

    transplant cuts.



    Lumonics (Canada) had been funding university research on

    the use of its excimer laser in surgical correction of the

    eye, but no recent references have been noted.


    Nidek (Japan) is reported to be investigating the use of

    excimer lasers in the treatment of ocular disease and in

    correcting vision.   Attempts to obtain more definitive

    information have as yet been unsuccessful.



    Synthelabo (France) showed an excimer laser at the 1988
    Academy of Ophthalmology Meeting in Dallas and is
 "White Paper on Sculpting"          page 13
September 15, 1989

    supposedly completing the development of its system.    They

    recently reported on animal eye studies but not as yet on

    humans.



IV. Results of the ADL/ORC Survey



As part of the recently completed study of the prospects for

"corneal sculpting", Arthur D. Little and its subsidiary,

Opinion Research Corporation, collaborated in seeking the

knowledge level and interest in corneal sculpting of the

ophthalmic community.   One thousand randomly selected

ophthalmologists, located in metropolitan areas, were sent a

comprehensive questionnaire that attempted to determine how

they felt about becoming involved in corneal sculpting once FDA

marketing approval was obtained.    One hundred and eighty nine

responses (19%) were received, of which 163 were included in

the tabulation of results, having been received before the cut-

off date.   The general findings are reported below.


o   Of the 163 tabulated respondents, 55% were in solo

    practice, 15% in partnerships and 25% participated in group

    practices.   The overwhelming majority, 72%, considered

    themselves "general ophthalmologists" as opposed to

    specialists, and they were fairly evenly split in terms of

    years in practice and location around the country.
 "White Paper on Sculpting"          page 14
September 15, 1989

o   Knowledge of our respondents regarding corneal sculpting

    was on the low side.   Eight percent knew little or nothing

    about it, and only 9% considered themselves very

    knowledgeable.    The remainder had either attended a seminar

    (13%), had heard about it (33%), or read about it (59%).

    Their impressions about the ophthalmic community's

    knowledge of sculpting was decidedly on the low side, with

    their belief that 76% of their colleagues had only slight

    to no knowledge about the technique.   They felt that only

    2% of their peers had a great deal of knowledge about the

    process, and only 21% were moderately knowledgeable.



o   In terms of interest in learning more on the subject, 67%

    of those surveyed were moderately to extremely interested

    in participating in the technology once it receives FDA

    marketing approval.    Ten percent were undecided and 9% were

    not interested.


o   Our respondents felt that the most important ophthalmic

    application for the excimer laser was for sculpting to

    correct myopia (65%), while 55% were in favor of ablating

    for correction of astigmatism, as compared to 37% in favor

    of T-cuts.   Correction of hyperopia and removal of scars

    was favored by 45%, while glaucoma filtration got a 51%

    favorable rating.
 "White Paper on Sculpting"         page 15
September 15, 1989

o   Most of the doctors (57%) would accept  1/2 diopters of

    correction for myopia and/or hyperopia, while an additional

    30% would accept  3/4 to 1 diopter accuracy.



o   Fifty-two percent said that they would charge between $1000

    to $1500 per eye, and an additional 29% claimed to be able

    to charge more than $1500.   On a weighted basis, a mean

    charge of $1360 would be charged, with a higher $1510 fee

    in the Northeast, and a lower fee of $1270 in the West.

o   The mean number of procedures that would be done per week

    was 4.9.   Only 28% expected to do 5 or more procedures per

    week, while 30% expected to do 2 to 4, and 21% thought that

    they would do one or less.



o   Acceptance of the procedure will only happen after it is

    reported on by their peers (27%), and/or in common practice

    (47%).   Only 15% reported that they would get involved

    either before general release (8%) or soon thereafter (7%).

								
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