Thursday, March 30, 2006

Customized Ablations #2: The Future is Close

This is the second of a series of eight articles chronicling the development of Customized Ablation or Wavefront Driven LASIK. This column contains my thoughts from the 1999 AAO meeting, and was published in the February 15, 2000 issue of Ocular Surgery News.

Customized Ablations: The Future is Close

Technology Update

Irving J. Arons
Managing Director
Spectrum Consulting

At last year's AAO meeting (1998), we learned of the first hints of customized ablations, as several firms announced plans to tie corneal topography to their lasers and use this diagnostic input to drive the ablation program. In addition, as I reported in the June 15th issue of OSN, Autonomous Technologies (Orlando, FL) was leading the way in going beyond topography to wavefront analysis, in other words, measuring all of the aberrations of the eye and using that data to not only achieve emmetropia, but to go beyond 20/20 vision and achieve "eagle-like" vision.

Well, technology has taken a major leap forward. Forget topography-driven ablations -- although it will make a difference in treating corneal defects like unequal/astigmatic corneas -- but wavefront/ray tracing analysis is closer than any of us thought. At this year's AAO meeting, I witnessed demonstrations on no less than three new wavefront and one new ray tracing devices. In addition, the Autonomous wavefront device, in conjunction with its LadarVision excimer, has now been used to treat human eyes, as Marguerite McDonald, MD, reported on the very early results of her first 5 patients, treated in September; while Theo Seiler, MD, of Dresden, Germany reported on his first dozen patients, treated in July and August, using his Dresden Wavefront Analyzer and the WaveLight (Erlangen, Germany) Allegretto scanning spot excimer laser. (The Dresden Wavefront Analyzer will also be used with a new small spot scanning laser about to be introduced by Schwind eye-tech-solutions GmbH of Kleinostheim, Germany.)

In addition to the Autonomous CustomCornea Measurement Device and the Dresden Wavefront Analyzer, to be developed and distributed by Technomed GmbH of Baesweiler, Germany, VISX (Santa Clara, CA) unveiled Josef Bille's 20/10 Perfect Vision (Heidelberg, Germany) wavefront device, and Bausch & Lomb Surgical (Claremont, CA) demonstrated a prototype of its aberrometer/wavefront analyzer (developed by Technolas GmbH of Munich, to be coupled with its Technolas 217C excimer laser, that appears to operate in a similar fashion to other wavefront devices. It is my understanding that the aberrometer will probable be incorporated into B&L's Orbtek (Salt Lake City, UT) Orbscan device, to provide maximum information about both the cornea and internal aberrations of the eye system. (Again, this was hinted at by Tim Turner of Orbtek, in his talk last Spring that I reported on in the June 15th issue of OSN.) I also saw a demonstration of a new ray trace device from Tracey Technologies (Bellaire, TX), formed by Joseph Wakil, formerly of EyeSys, to commercialize this new device developed at the Institute of Biomedical Engineering in Kiev, Russia. The device was discovered by Ioannis Pallikaris, MD, of Greece, who used it to run some of the first experiments on human eyes at the University Hospital of the University of Crete, and is a co-founder of Tracey Technologies. The Tracey device is an electro-optical interferometric analyzer that measures refraction in real time, to ±0.20 diopters, and according to its developers, may be more versatile in measuring aberrations of the eye than the wavefront devices.

So, instead of being overwhelmed by topolinked lasers, I was overwhelmed instead by the next generation of analyzers, wavefront and ray tracing. It appears that some of these devices will be available as soon as this Spring's ASCRS meeting, as a diagnostic tool to gather more complete refraction information, i.e., a better refraction, which can than be fed into current excimer laser's ablation programs for achieving a higher percentage of 20/20 corrections than can be done today. However, it will probably be several years before wavefront-linked customized ablations will be routinely available for general use. In the meantime, topographic links are still moving forward, with several laser companies not yet working with wavefront technologies, striving to establish relationships with topography companies or devices. (See the accompanying table for listing of which analytical/diagnostic devices each of the excimer laser companies is currently pursuing.)

The New Technologies

Summit Technology/Autonomous Technologies

Autonomous has spent over three years working on its CustomCornea wavefront measuring device. These efforts are starting to bear fruit, with the first patients treated using the system, and the FDA accepted the company's IDE for CustomCornea last July. The first of 40 patients have been enrolled in a Phase II-like feasibility study to determine calibration and safety, with doctors treating one eye with LASIK, and the other with CustomCornea-controlled LASIK. In Dr. McDonald cases, she was able to objectively measure the unique aberrations of each patient's eye and treat the CustomCornea eye with an individualized ablation pattern to correct for those aberrations. Autonomous expects that it will take 1 to 2 years to complete its Phase III clinicals and be ready to submit data to the FDA. However, the company expects to be able to market a stand-alone diagnostic device sometime next year, which laser users will be able to use to achieve better refractions to feed into the laser's ablation program.

Autonomous believes that it has an advantage over others working with wavefront technologies, because of its LadarVision system and its unique eye tracker. The company believes that the combination of a small spot scanning laser and the ability to place the correction precisely where it is needed gives it a step up on its competition.

VISX/20/10 Perfect Vision

At a presentation sponsored by VISX, Josef Bille, the founder of 20/10 Perfect Vision, explained how he got involved in developing his wavefront analyzer, which will be marketed by VISX under an exclusive worldwide agreement. Bille, the Director of the Institute of Applied Physics at the University of Heidelberg, and a founder of both Heidelberg Engineering and Intelligent Surgical Laser (ISL), originally developed the technology for use in astronomical applications in the mid 1970s, with the first German patents filed in 1982 and issued in 1986. In 1997 through 1999, he co-founded 20/10 Perfect Vision, and filed additional patents covering his later developments. The technology is based on adaptive optics to compensate for aberrations, using a deformable mirror, which has been reduced in size to a microchip array today, and speeds up the testing time to less than 15 seconds. A laser signal is imposed onto the retina and the return signal is analyzed using a CCD device to form an acuity map and a differential acuity map, which are used to achieve a simulation of best acuity. In this way, the device can analyze the refractive state of the eye, and the output can be used to make a more exact contour ablation of the cornea. VISX intends to incorporate the technology into a diagnostic device, which they hope to make commercially available in 2000.

The real question is how VISX intends to couple the diagnostic tool to their laser. According to experts in the field, a rapid firing, small spot scanning laser is needed to place a precise ablation pattern on the cornea, and a rapid-response tracking device is needed for this precise placement. VISX currently can scan a small spot, but at a rather slow scanning rate (50 Hz), and does not, to my knowledge, have a precise tracking device for their laser system. Perhaps, they will acquire the needed technologies in order to commercialize their wavefront technology for performing customized ablations.

According to a VISX spokesperson, the company plans to deliver active eye tracking and rapid small spot scanning capabilities in fiscal year 2000. The STAR S2 has already demonstrated its ability to deliver ablations as small as 1 mm in diameter via its CAP Method for the treatment of irregular corneas (currently available for international use only). Theoretically, it would not even be necessary to complete an entire custom ablation with a small spot, but rather through a combination of broad area (not beam) ablations followed by small-spot "contouring" method.

The Dresden Wavefront Analyzer/TechnoMed Technology

Developed by Theo Seiler and his colleagues at the Department of Ophthalmology, University Eye Clinic, Dresden, Germany, the Dresden Wavefront Analyzer is based on the Tschernig aberroscope, first described in 1894. A bundle of equidistant light rays are projected onto the cornea, and due to optical imaging, become focused on the retina. In an aberration-free eye, the retinal image pattern consists of equidistant light spots. However, the spot pattern of a normal eye is distorted, according to the ocular aberrations. The deviation of all spots from the ideal pattern is measured by an indirect ophthalmoscope and directed to low-light CCD linked to a computer, and these patterns are used to compute wavefront aberrations in the form of Zernike polynomials. When compared with and integrated with pre-operative corneal topography, an ablation profile is computed and used to feed the excimer laser to correct for all of the eye's aberrations. By reducing the ocular aberrations, and adjusting for the differential effects of the pupil size, the visual acuity can be dramatically improved, approaching 20/15 vision or better.

The Dresden Wavefront Analyzer uses a frequency-doubled Nd:YAG laser at 532 nm and a mask system to create 168 equidistant and parallel light rays for projection onto the cornea. The overall exposure time is 40 ms. The precision of the device allows for an objective measurement of spherical and cylindrical refractive error with an accuracy of better than ±0.25 diopters.

The device will be marketed by TechnoMed Technology and will be coupled with excimer laser systems from both WaveLight Laser Technologies AG and Schwind eye-tech-solutions GmbH.

WaveLight Laser Technologies AG

The Dresden Wavefront Analyzer has been used with WaveLight's Allegretto excimer laser to treat the first human patients, beginning in March 1999. In July, Professor Dr. Theo Seiler used the system to treat the first patients under the WaveLight protocol. The post-operative vision of the first seven patients was 2-3 times as sharp as that of a normally-sighted (20/20)person. Of the first 12 patients treated, 3 have achieved 20/15; 2 are at 20/10; and 1 had achieved 20/8. Anecdotaly, Dr. Seiler told of the woman that he had treated who reached 20/8 acuity. The doctors in attendance were overwhelmed by her visual acuity but, the woman complained that she was unhappy with her new vision, as she could no longer watch television. It seemed that instead of seeing the clear pictures on the screen, she was now seeing the raster lines! Since then, additional patients have achieved 20/8 acuity without that particular problem.

It is expected that the use of the Dresden Wavefront Analyzer in conjunction with the WaveLight Allegretto laser will be able to achieve visual acuities of 20/15 routinely, and possibly be able to achieve some acuities of 20/10, and possibly to the retinal diffraction limit of 20/6.

The WaveLight Allegretto laser is a small spot (1 mm) scanning system. It operates at 200 Hz repetition rate, and utilizes a 250 Hz active tracking system, based on an infrared camera. The tracker is pupil-based, and uses a patented illumination system to guarantee stable tracking through all stages of surgery, independent of ablation type or quality of the keratome cut. It can be selected for self-centering of the pupil center, or decentered as desired.

WaveLight is undertaking a European study of low to moderate myopia with astigmatism at 3 sites in Germany, Spain and Ireland, that will be done according to FDA protocols, for possible use in an FDA submission for U.S. marketing approval. 150 patients from -1 to -10 diopters, with 0.25 to 2 diopters of astigmatism will be included. The Dresden Wavefront Analyzer will be used on both eyes and bilateral LASIK performed, using the Chiron Hansatome, the Schwind Supratome, and the Moria CB keratome.

Schwind eye-tech-solutions

As previously noted, the Dresden Wavefront Analyzer will also be utilized with a new Schwind 6th generation scanning small spot excimer laser with active tracking. The laser will operate at 200 Hz and have a 250 Hz passive/active eye tracker, which corresponds to a reaction time of 4 ms. The local pulse repetition on a single point will be less than 35 Hz, in order to avoid local heating of the corneal tissue. It is expected that the ablation area will be quite smooth, created by a small 0.9 mm gaussian laser spot. The system will combine all standard treatments, along with customized ablations based on either topographic or aberrometric diagnostic information. According to Dr. Seiler, this new laser creates the smoothest ablations that he has seen. It is expected to be unveiled at this Spring's ASCRS meeting, at which time more details will be available.

Bausch & Lomb/Chiron/Orbtek

Not much technical information was provided about the new aberroscope being developed by B&L for use with its Chiron/Technolas excimer laser. The device demonstrated appeared to be a Hartmann-Shack type system, operating in a similar fashion as those from Autonomous, 20/10 Perfect Vision, and Dresden. Similar ablation maps were created, but no details of how this device would be linked to the Technolas laser. It is assumed that the analyzer will be combined with Orbtek's Orbscan corneal topography device, to provide total cornea and eye system aberration measurements. No information was provided about whether Bausch & Lomb intends to commercialize the aberroscope as a separate-standing diagnostic system.

Tracey Technologies

The final device shown on the AAO exhibition floor for measuring the abnormalities of the refractive system of the eye was the Tracey Ray-Tracing Refractometer. Unlike the Hartmann-Shack type devices, the Tracey ray tracing device uses the fundamental thin beam principle of optical ray tracing to measure the refractive power of the eye on a point-by-point basis. According to Tracey Technologies, its ray tracing device measures one point in the entrance pupil at a time, rather than measuring the entire entrance pupil at once, like the aberroscopes and Hartmann-Shack devices, with the possibility of data points criss-crossing with a highly aberrated eye. The ray trace device is designed to very rapidly fire a series of parallel light beams one at a time, within microseconds, into the eye, passing through the entrance pupil in an infinite selection of software selectable patterns. With this technique, the Tracey system can probe particular areas of the aperture of the eye. By design, the Tracey system can register where each "bullet" of light strikes the retina as the fovea is represented by the conjugate focal point of the system from the patient's fixation. Semiconductor photodetectors are able to detect the location of where each light ray strikes the retina and provide raw data measuring the (x,y) error distance from the ideal conjugate focus point, giving a direct measurement of refractive error for that point in the entrance pupil. Because of the high speed of the system, 64 points of light within a 6 mm pupil can be measured five times each in just over 10 ms, thus greatly increasing the accuracy and reproducibility of the system. The Tracey system can easily measure a large dynamic range of aberrations and maintain high resolution, which should provide for a significant advantage when measuring a physiological system, such as the eye, with its range of refractive errors. The Tracey system is practically a direct measure of the point-spread function of the eye, and with its retinal spot detection, can easily provide for full calculation of wavefront deformation and modulation transfer function of the eye.

Tracey Technologies expects to have its device ready for commercialization within three to six months, and for it to be priced in the range of a premium topographer.

Although all three of the techniques for measuring the aberrations of the eye -- the aberroscope, Hartmann-Shack analyzer, and the ray tracing device -- can provide a map useful for determining ablation patterns, Tracey claims that its device has a greater speed of measurement, greater reproducibility, and more flexibility through simple software selection of the desired data points of measurement. Only time will tell which type of device is preferred by the marketplace.

Techniques Under Development/in Use for Customized Ablations

Company           Wavefront   Corneal Topography Topography +
Aesculap-Meditec X X Autorefractor
B&L/Technolas X X
LaserSight X
Nidek X
Schwind X X
Summit/Autonomous X
Telco X
WaveLight X X

Source: Spectrum Consulting, December 1999.

Customized Ablation #1: I've Seen the Future....and it's CustomCornea!

This Technology Update column is the first of a series of eight articles chronicling the development of Customized Ablation or Wavefront Driven LASIK. This column was published in the June 15th issue of Ocular Surgery News following both the 1999 ASLMS (American Society for Lasers in Medicine and Surgery) and ASCRS (American Society of Cataract and Refractive Surgery) meetings.

I've Seen the Future.....and it's Custom Cornea!

Technology Update

Irving J. Arons
Spectrum Consulting

What if you could more accurately predict and successfully restore a patients vision to 20/20 with refractive surgery. What if, in some cases, you could actually achieve "Ted Williams" type vision (20/16) or better for your patients who would want that. Would you be interested in finding out more?

Since I first heard Marguerite McDonald's presentation on custom cornea at last fall's AAO meeting (1998), I've been intrigued with the idea, and have wanted to know more about how it was going to be accomplished. The idea of not only correcting vision to emmetropia (20/20), but enhancing it to 20/16 or better was exciting and this was only reinforced by the presentations given at a Bausch & Lomb press conference at the AAO, where George Waring declared 20/12 by 2012, now changed to 20/10 by 2010 in current B&L Surgical advertisements! (For more on both of these presentations, see my columns from the AAO in the January 1st issue of OSN.)

Now, after hearing a presentation given by Tim Turner, director of research at Orbtek, on the "Orbscan Corneal Topography Laser-Link System" (at the recent American Society of Lasers in Medicine and Surgery [ASLMS] meeting in Orlando), and especially after viewing a tape of a course given at the recent ASCRS meeting by Marguerite McDonald, Ronald Krueger, Ray Applegate and George Pettit on "Wavefront-Guided Customized Ablations -- Beyond Topography-Assisted Refractive Surgery", sponsored by Autonomous Technology -- now a subsidiary of Summit Technology, I am convinced that topographically-linked ablation, and especially wavefront-guided ablations, are the future of refractive surgery.

As reported last January, several companies have announced that they are in the process of combining corneal topography with their excimer laser systems to be able to perform "custom" ablations. Among those are LaserSight, working with Humphrey-Zeiss and Orbtek; VISX, working with EyeSys Premier and Orbtek, among others; B&L Surgical/Chiron with Technomed and Orbtek; Schwind with Technomed; and Aesculap-Meditec, also with the Orbtek system and possibly Technomed.

In Dr. Turner's presentation, he explained how the first-generation of topographically linked laser ablations, which depend on the capture of topographic information (corneal curvature and elevation) supplied by such placido reflection systems as Computed Anatomy and EyeSys Premier, will probably be the first out of the block, along with the Orbscan slit scanning system. The Orbscan is capable of providing additional information such as the thickness of the cornea and the condition of its rear surface, through what Orbtek calls CIPTA, or Corneal Interactive Programmed Topographic Ablation. However, by combining the Orbscan with ultrasound to determine the ocular axial length and lens thickness, a simulation of the retinal point spread function (PSF) can be determined. Point spread functions can be calculated for any surface or any sequence of surfaces. Thus a PSF can be calculated from anterior corneal data alone, but it may or may not approximate the true retina PSF, depending on the optical importance of the other internal ocular surfaces. However, this does not include local aberration-inducing variations. So, Orbtek has created a simulated next-generation measurement technique called WAVE, or Wavefront Ablation Vision Enhancement. WAVE treats patient vision rather than corneal geometry (elevation and surface curvature), by targeting idealistic post-operative surface topography with the optical PSF optimized. It calculates wavefront aberration by reverse ray tracing of all of the rays emanating from a theoretical point source of light at the fovea and back through a modeled crystalline lens and the measured cornea. Orbscan measurements are used by WAVE to fully characterize the cornea (both anterior and posterior surfaces), and other data (refraction, ultrasonic axial length and lens thickness) are used to model the crystalline lens. These additions aid in the simulation of the true retinal PSF and the ocular wave aberration. When wave aberrations are directly measurable, they can also be included in the WAVE strategy. The WAVE system is still experimental and has not yet been used on any human patients.

The major difference between what Orbtek and Autonomous Technology are attempting to do is in the measurement of aberrations. As noted above, Orbtek uses theoretical measurements and modeling to simulate an aberration pattern, while Autonomous actually measures the total aberration of the eye by shooting a laser pulse onto the retina, through the lens, and obtains an actual aberration pattern of the return waves, thus getting a more accurate pattern of what aberrations are present in the complete optical system.

Autonomous uses a proprietary wavefront sensor to capture the wavefront pattern returning from the laser-induced spot on the retina. It then converts this information into a 3D map of the aberrations to determine what changes are needed in the corneal surface to compensate for the aberrations present in the eye, and to overcome them. Autonomous has built a prototype device, called the CustomCornea Measurement Device, and, under an IRB, has placed it in an ophthalmologist's office in Florida in order to take measurements on patients under a real-life situation, beginning in April. In an in-house study of 103 eyes, including some people with 20/20 or better vision and some with known pathologies, the custom cornea maps provided by a prototype device, appeared to bear out the theory -- emmetropes, as well as those with sharper vision have less aberrations and can be distinguished from those with aberrated vision. In the near future, this information will be programmed into the LadarVision small spot scanning laser system to provide the potentially enhanced vision, possibly reaching the theoretical diffraction limits of the retina of 20/8!

Of course, all of this would not be possible without the extremely accurate tracking system available on the Autonomous laser. Since the accurate placement of the "compensating" ablation pattern is necessary, by linking the wavefront analysis device to the LadarVision tracking laser, the precise pattern of ablation correction can be obtained, centered on the visual axis, and "customcornea" achieved. The company hopes to begin CustomCornea treatments this summer, depending on regulatory approvals and, hopefully, within the next two years, this technology could become a commercial reality.

Editors note: This column was not put online by OSN. The Janury 1st column mentioned, is also not online, but was picked up by a sister publication, OCULAR SURGERY NEWS EUROPE/ASIA-PACIFIC EDITION, and published in February 1999. (Which is linked.)

Monday, March 27, 2006

Inlays, Onlays, Rings & Things – Part 2

Following the 2000 ASCRS Meeting, held May 20-24 in Boston, I wrote a meeting roundup concentrating on the (then) new developments in technologies besides laser, that were presented at that meeting. Here is the column I wrote for Ocular Surgery News that appeared in the July 15, 2000 issue.

ASCRS 2000 Roundup

Irving J. Arons
Managing Director
Spectrum Consulting

The annual ASCRS symposium on cataract, IOL, and refractive surgery was held at the Hynes Auditorium in Boston, May 20-24, 2000. More than 10,500 attendees, including about 7000 physicians and other medical personnel, along with about 3500 exhibitors, heard presentations covering a range of ophthalmic topics from the latest in IOLs and phacoemulsification for cataract surgery (including laser phaco), to the newest techniques for performing refractive surgery. There were also presentations on treatments for glaucoma and retinal disease, including the newly approved Visudyne therapy for halting "classic" age-related macular degeneration.

As usual, I concentrated on two areas: the latest developments in laser refractive surgery; and on new technologies that may impact ophthalmology in the years ahead. In refractive surgery, the emphasis at the meeting was on how all of the laser companies are now including some form of diagnostics (wavefront or other) for evaluating the eye and using that information, i.e., a better refraction, for performing LASIK. I conducted a survey of all the major U.S. and international laser companies to determine the specifics of their lasers, trackers -- where available, and the diagnostic device(s) they intend to use to perform customized ablations. The survey results will be available next month.

This month, I would like to inform you about some of the interesting new technologies presented, some of which are in clinical trial, while others are just beginning to be developed. I believe that many or all may have an impact on ophthalmology in the future.

Inlays, Onlays, Rings & Things

Ten years ago, in 1990, following that year' ASCRS meeting, I wrote a column for the May 1990 Ophthalmology Management with the above title. I described some of the interesting approaches to correcting vision, from the mild renewed interest in RK, probably brought on by the then intense interest in PRK, and the inability of a large number of physicians to get involved in the ongoing clinical trials, to a renewed interest in other means for shaping the cornea. Some of the advances underway included various forms of epikeratophakia using inlays and rings, made of both hard and soft plastics; onlays made of both human tissue and synthetic lenticle materials; and the advances being made in both standard and multifocal IOLs for use in phakic eyes. At the time, there were also presentations about the possibility of injecting either a hydrogel or silicone material into a cleaned out capsule via a small injection hole, to provide an injectable, accommodating lens for treating presbyopia.

Some of the epi-inlays, both collagen and hydrogels, in addition to cryolathed human tissue, included lyophilized donor corneal tissue (the Kerato-Lens and Kerato-Patch) from Allergan Medical Optics, a hydrogel called Kerato-Gel from the same company, and a hydrogel from Alcon Surgical. The IOL company, Surgidev, was sponsoring trials on a microperforated nutrient and gas permeable polysulfone material, while Optical Radiation had developed a fresnel hydrogel intracorneal lens, and the KeraVision intracorneal ring trials were still in pre-clinical trials.

As for onlays, Chiron Ophthalmics and GE Medical Systems were sponsoring programs to place either hydrogel or collagen onlays on de-epithelized cornea and have the epithelium grow back over the onlay to hold it in place. (Don't forget that there were no meaningful microkeratomes available at that time.) GE's program was underway at Emory University and involved an excimer laser, in a program called LASE (Laser Adjustable Synthetic Epikeratoplasty) with a collagen onlay supplied by Domilens. The theory was that the onlay would be placed on the cornea and reshaped as needed by the excimer laser prior to re-epithelization.

And then there was the injectable lens. Innovative Surgical Products, under the sponsorship of Allergan Medical Optics, was working on a method to inject an enzyme into the capsule to dissolve the cataractous lens, followed by injection of a liquid polymerizable silicone polymer, that would fill the capsule and provide accommodation. (Low level efforts at developing an injectable lens remain ongoing, but not by ISP or Allergan.)

Of all of these interesting technologies, only the KeraVision rings ever made it into commercialization, and that, only within the past few years. However, similar devices/programs as described ten years ago, are still being worked on today.

As I wrote back then, in the field of surgical vision correction, lasers may have had the spotlight, but a lot was going on in both the footlights and backstage, which leads me into what I discovered this year. Again, the spotlight is on laser vision correction, especially with the future potential of customized ablations, but innovative technologies are still being developed that could have an impact on vision correction over the next decade.

Inlays, Onlays, Rings & Things: Part Two

Although not an intra-stromal inlay, today's implants include the collomar ICL (implantable contact lens -- that is inserted in front of the natural lens) from Staar Surgical, for correcting high myopia, in Phase III clinical trials, and a new attempt at a microporous intracorneal lens inlay called the PermaVision Intracorneal Lens. It is made from a proprietary, patent allowed, 78% water content biocompatible hydrogel called Nutrapore. Produced by Anamed Inc., the 4.5 to 6 mm diameter micro-precision meniscus-shaped lenticle has an edge thickness of 10 microns, and a center thickness of 30 to 50 microns, for correcting hyperopia, by steepening the cornea. According to the company, the hydrogel mimics the stroma, having an identical refractive index to avoid optical aberrations or glare, and because of its microporosity and high water content, allows fluids, gases, and nutrients to flow freely through it, to nourish the front of the cornea. The lenticle is put in place by forming a flap with any microkeratome, placing the lens carefully, without decentration, over the pupillary axis, and closing the flap. Obviously, if needed, the lens can be repositioned, replaced, or removed simply by lifting the flap, making the procedure adjustable and reversible (similar to the KeraVision Intacs). To date, 11 animal eyes with up to 12 months followup, and 8 human eyes with 5 months followup, have been implanted at 3 sites in 3 countries, with corrections varying from +2.25 to +6.75. Clinical trials will be expanding over the next several months, to new sites in Europe, the Middle East, South America and Canada signed on for the study.

In addition to treating hyperopia, the company has plans for treating myopia, hyperopic astigmatism, and for presbyopia, the latter with a bifocal lens design. According to company officials, TLC Laser Eye Centers was an early investor.

On the onlay front, a newly formed company, MedRx Technologies, founded in 1999, has entered into contracts to acquire Imperial Medical, a manufacturer and distributor of IOLs; C-Scan, the corneal topography system from Technomed, and Inpro Laser, a German excimer laser company. In refractive surgery, the company intends to provide the means for custom optical profiling, incorporating ReFrax, a collagen corneal masking gel (from Imperial Medical), that will be used in conjunction with any excimer laser (including the company's) to reshape the corneal surface. In use, the gel is applied to the cornea's surface, an applinator (a sophisticated collagen mold customized for each patient -- similar to a hard contact lens) is placed on top of the gel, which hardens in about 15 seconds, attaining the shape of the mold. The surgeon than uses an excimer laser to photoablate layers of the hardened gel, to attain the desired new corneal shape. The company hopes to begin distributing the product internationally during the third quarter of this year, and to begin U.S. clinical tests in mid- to late-2000. Training of European and South American surgeons is scheduled for this summer. The ReFrax system will sell for approximately $700 to replace corneal transplants, and for about $250 for standard refractive surgery.

In terms of rings, I learned that KeraVision has designs not only on low to moderate myopia correction, but also for astigmatic correction with partial or shorter ring segments, and also for hyperopic correction with the placement of 4, 6, or 8 radial segments aligned similar to RK cuts.

Other "things" picked up by walking around the exhibit hall and attending the Technology Forum sponsored by Medical Laser Insight, included both a new laser method for treating hyperopia, the 1.9 micron diode laser from Rodenstock, that is owned by ProLaser Medical Systems, and a non-laser technique from Refractec; new advances made by IntraLase with its femtosecond laser, both for use as a microkeratome and for ablating tissue within the stroma; some insight (but only a little) into what JT Lin and Surgilight is planning to do in treating presbyopia with his infrared laser system; and a little about how C&C Vision plans to overcome the problems involved with its accommodating IOL.

In addition to the PermaVision ICL mentioned above, Refractec (with its RF [radio frequency] energized tiny probes) and ProLaser with its diode laser, along with Sunrise Technology and its holmium laser system, are all seeking to take over the treatment of hyperopia from excimer lasers. Refractec's ViewPoint CK (conductive keratoplasty) system uses tiny probes that are inserted 80% into the cornea's thickness to cause a thermal column of collagen shrinkage to provide corneal steepening for hyperopia (and, via monovision, for presbyopia). According to Marguerite McDonald, the treatment time totals about three minutes, with either 8 or 16 spots are treated, each taking about 0.6 seconds, once the hand-held probe is positioned and inserted into the cornea. Some 400 patients have been treated to date, ranging from +1 to +4 diopters. The device is expected to sell for about $40,000, plus a $100 per procedure charge.

The Rodenstock DTK system (diode laser thermal keratoplasty), produced by ProLaser Medical Systems, also uses a handheld contact probe (without penetrating the cornea) that focuses the laser's energy into the stroma, supposedly providing a more controlled, deeper release of the thermal energy to gain more predictable results with less regression as compared to the non-contact system from Sunrise. This small, compact diode laser will sell for about $50,000, much less than the anticipated $250,000 system from Sunrise. U.S. clinical trials are expected to begin shortly. There are more than twenty Rodenstock diode DTK lasers in use in Europe, with more than 600 patients successfully treated. ProLaser Medical Systems was established earlier this year, with the purchase of the assets of Rodenstock Instrumente GmbH, including the DTK laser program. The company has decided to retain the Rodenstock name because of its reputation.

An interesting innovation on the new Sunrise Hyperion laser is internet connectivity. This allows the company to perform per procedure billing, but also allows collection of patient treatment and outcomes data. If the laser user adds in the pre-op and postop data from each patient, the compiled data base becomes accessible by new doctors, or previous users each time a new patient is treated, providing an updated algorithm for treatment of a patient fitting the same or a similar profile. This appears to be a innovative way of compressing the learning curve.

IntraLase has made considerable progress in developing its femtosecond laser, now called the Pulsion FS, with its recent 510(k) FDA approval for use as a laser microkeratome. A planar cut takes about one minute to accomplish, with plans to do it faster in the works. The only problem, at least as seen in the demonstration video, is that the flap (or lenticle, when used to create a lenticle within the stroma for intrastromal ablation) appears to "stick" to the stromal tissue, and is difficult to remove. Perhaps a lubricant to separate the tissue is needed. An additional application, expected before commercial introduction at this year's Academy of Ophthalmology meeting, is clearance for creating the channel(s) for Intacs insertion. Currently, the creation of a removable intrastromal lenticle takes between 2-2½ minutes, compared to 20 to 40 seconds for excimer laser ablation (after flap formation). The laser will be sold on a per procedure basis when it becomes available.

In a not easy to understand presentation, JT Lin of SurgiLight attempted to describe what his company was doing in attempting to correct presbyopia. All that could be determined was that the company was conducting trials in Venezuela using its IR 3000 infrared laser to either ablate or coagulate tissue in the sclera to create more space for the natural lens to accommodate, similarly to what Presby Corporation does with its plastic scleral bands. However, since the Venezuelan physicians were apparently not following any type of protocol, the results obtained were not very meaningful. We will just have to wait and see if anything comes from this laser approach.

Last, but not least, Bill Link, formerly the head of Chiron Vision before it was sold to Bausch & Lomb, and now running a venture fund (Versant Ventures) funding ophthalmic innovation, spoke about C&C Vision, and its accommodating lens for treating presbyopia. The lens is a bi-hinged IOL positioned in the back of the lens capsule that, during reading, the ciliary muscles can "push" the central optics forward to provide accommodation. More than 80 lenses have been implanted to date, with good results. The major problem to be overcome is the need for keeping the lens stationary during the healing/seating period following insertion. This is now done by applying atropine drops for several days to immobilize the ciliary muscles, and thus not push the whole lens out of position. More clinical testing remains to be done to see how long the immobilization period must be for this lens to work properly.

In summary, in addition to all of the excitement about "customized ablation" refractive surgery, there were other interesting developments taking place at ASCRS. I hope I was able to capture some of the highlights for you.


Jennifer Webb, writing in the February 15th issue of Ophthalmology Times, reported that George A. Williams, MD, a vitreoretinal specialist in private practice in Royal Oak, MI, and chairman of the department of ophthalmology at William Beaumont Hospital, speaking at Macula 2006 in New York City in January, said that, “Ophthalmologists who choose to use bevacizumab (Avastin, Genentech) for off-label treatment of wet age-related macular degeneration (AMD) should not expect Medicare to reimburse those expenses.”

When he polled the 300 attendees at the meeting, on whether they had tried Avastin, “Ninety percent of the hands went up. I've never seen anything like this in 25 years of medicine: how quickly this has permeated the field and how quickly it's being adopted."

In a Dec. 21 article posted on Medscape, Jennifer I.. Lim, MD, explained that bevacizumab offered symptomatic relief from active subfoveal choroidal neovascularization (CNV) in a high percentage of patients, and its intra-vitreal use has increased "exponentially" in the past few months.

"Positive presentations at retinal meetings and the two published case reports of visual acuity improvement and decreased retinal thickness have led the retinal community to embrace this new treatment," Dr. Lim wrote. She is associate professor of ophthalmology, University of Southern California, and medical director of clinical trials, Doheny Eye Institute, Los Angeles.

Weighing off-label use

Despite this interest over bevacizumab, insurance carriers and Medicare are not as enthusiastic. Aetna, for example, listed the drug in late November as experimental and investigational—and not medically necessary—for the treatment of AMD.

"Carriers decide whether they're going to cover an off-label use based on a variety of evidence such as published trials, clinical trials, and published reports. [Bevacizumab] has moved so quickly [that] we still don't have publications out," Dr. Lim said. "Until they see these publications, their decision will be they can't cover it."

William Rich III, MD, medical director of health policy for the American Academy of Ophthalmology (AAO), said many accepted procedures and treatments are used off-label. He cited the National Institutes of Health-sponsored clinical trials that recommend injection of intravitreal antibiotics to treat endophthalmitis as one example.

Dr. Rich said bevacizumab is an appropriate drug to use as "salvage therapy" after other treatments have failed. Although Medicare does not yet reimburse for bevacizumab therapy for AMD, most patients are willing to pay the cost, Dr. Rich said. The drug costs $20 to $80 per treatment, he said.

However, two reports on the safety and efficacy of bevacizumab injections are expected to be published soon, he said. After that happens, AAO leaders and retina specialists will ask the Centers for Medicare and Medicaid Services to cover those treatments, as it does for off-label use of triamcinolone to decrease the need for photodynamic therapy and uveitis injections around the eye.

"There's not enough literature to justify [covering the] treatment at this time," Dr. Rich said, adding that the AAO also supports a head-to-head comparison of bevacizumab and ranibizumab (Lucentis, Genentech).

"Once a treatment is approved, physicians can use it and prescribe it how they see fit," said Genentech spokeswoman Dawn Kalmar. However, she said, "we are concerned, because we specifically designed ranibizumab to avoid some of those things that may or may not happen with a full-length antibody such as bevacizumab. The company has never performed any trials, animal testing, or toxicity testing using bevacizumab in this manner, so it is "concerned."

"From our perspective, that points to a significant unmet need that's still out there," Kalmar said. "People are willing to try it because there really is no hope for many of these patients. Our primary stance is: we're doing everything we can to get ranibizumab into the hands of physicians and patients as soon as possible."

For example, the company filed Dec. 30 for priority review status for ranibizumab with the FDA. Kalmar said Genentech should know within 6 weeks of that date if that status is granted. Once prior review status is achieved, Genentech would hope to have approval for the drug later this year.

She also pointed to the opening of a phase IIIb, single-masked, 1-year multicenter study of the safety and tolerability of intravitreally administered ranibizumab in patients with active subfoveal choroidal neovascularization (CNV) secondary to AMD. The trial, which began in November 2005, will enroll 5,000 patients at 70 sites nationwide, giving physicians an opportunity to try the new drug before FDA approval, she said.

As a full-fragment antibody, bevacizumab might not penetrate as well as researchers believe ranibizumab will, she added.

"When we tested a full-length antibody, it didn't penetrate as readily to get to the root cause of where the disease was," Kalmar continued. "One of the reasons we did a small fragment [version] was to penetrate to all the layers of the retina to get to where the disease starts."

When the most recent ranibizumab data were presented at the Macula 2006 meeting, "I literally saw jaws drop," she added. "We're very pleased both on the efficacy and safety side of ranibizumab and we're looking forward to getting it out there."

Author’s Note on Avastin

Since the original posting on January 31st, I have added three updates on this important drug for treating age-related macular degeneration. In addition to the posting you are reading, here is a listing (with links) to the others:

Avastin: A New Hope for Treating AMD

Avistin Update II: AAO supports Medicare Coverage for Off-label Avistan Use

ARVO 2006: A Further Update on Both Avastin and Lucentis for Treating AMD

Menu - Part 4: A Fourth List of Publications for Potential Posting

First, two updates on previously published items:

Avastin Update: Medicare not Likely to Cover its Use

Following posting of the original article – Avastin: A New Hope for Treating AMD, I found an online article that clarifies the Medicare position on “off-label” usage of this drug.

Inlays, Onlays, Rings & Things - Part 2

The original article was written in 1990. Following the 2000 ASCRS meeting, I updated my findings on these types of devices.

As part of my coverage of both the AAO and ASCRS annual meetings, I sat in on the technical presentations and also spent several days walking the vast exhibit halls, gleaning information on new developments in both lasers and other ophthalmic technologies.

Customized Ablation/Custom Cornea: Wavefront Driven LASIK (WFL)

Before presenting my reports on several of these meetings, I would like to showcase two important technologies that I was among the first to write about: Customized Ablations (or Wavefront Driven LASIK), and LASEK, the technique of pushing aside the epithelium and performing PRK on the surface of the cornea – as opposed to first making a flap with a microkeratome or laser, and then zapping the cornea to reshape it.

Here, in chronological order, is a series of writeups on these techniques:

1. I’ve Seen the Future....and its Custom Cornea, OSN, June 15, 1999.

I first learned about custom ablation at the 1998 AAO meeting, but it was at the 1999 ASCRS meeting that I came to realize that it was the future of refractive surgery.

2. Customized Ablation: the Future is Close, OSN, February 15, 2000.

My first encounter with wavefront and ray tracing diagnostics as a pre-cursor to customized ablation.

3. Customized Ablation: Getting Closer Yet, OSN, August 1, 2000.

At the 2000 ASCRS meeting I learned first-hand of the early results on the initial human clinical trials using wavefront combined with LASIK.

4. Customized Ablation: The Wave Moves Forward.....but Keep an Eye on a Newly Developed Technique....LASEK!, OSN, January 1, 2001.

My first exposure to LASEK – laser epithelial keratoplasty, as I explained it in detail.

5. AAO Report: LASEK, Customized Ablation Draws Interest, OSN, January 1, 2002.

More results from ongoing custom LASIK trials and a new technique for performing LASEK.

6. AAO Refractive Pre-Meeting Focuses on LASIK, LASEK, OSN, January 15, 2002.

An overview of what was reported at the RSIG pre-AAO meeting.

7. ASCRS Report: Customized Ablation, Hyperopia & More, OSN, August 1, 2002.

An overview from the 2002 ASCRS meeting.

8. An AAO 2002 Update: Classic vs. Custom LASIK -- The Battle Continues, OSN, January 1, 2003.

And finally, my last report for OSN, reviewing the latest developments occurring at the 2002 AAO meeting.

9. Custom Ablation #9: Questions......and Answers (May 5, 2006)

An update and answer on the question – Custom vs Classic Lasik.

Wednesday, March 22, 2006

ADL Chronicles – Of Silk Purses and Lead Balloons

This posting has been moved to a separate blog – ADL Chronicles. Please click on the link to get there.

Of Silk Purses and Lead Balloons

Tuesday, March 21, 2006

ADL Chronicles -- An Erasable Ink Composition

This posting has been moved to a separate blog – ADL Chronicles. Please click on the link to get there.

An Erasable Ink Composition

ADL Chronicles -- An Improved Firefighter's Glove

This posting has been moved to a separate blog – ADL Chronicles. Please click on the link to get there.

An Improved Firefighter’s Glove

Friday, March 17, 2006

ADL Chronicles -- The Disposable "Motionless Mixer"

This posting has been moved to a separate blog – ADL Chronicles. Please click on the link to get there.

The Disposable “Motionless Mixer”

ADL Chronicles – Spin-cast Eyeglass Frames

This posting has been moved to a separate blog – ADL Chronicles. Please click on the link to get there.

Spin-cast Eyeglass Frames

Wednesday, March 15, 2006

ADL Chronicles -- The EPCON Plastic Pencil

This posting has been moved to a separate blog – ADL Chronicles. Please click on the link to get there.

The EPCON Plastic Pencil

The Nature and Evolution of the Soft Contact Lens Industry in the United States

During the early years of my consulting career at Arthur D. Little, Inc., before specializing in ophthalmic and medical lasers, I became an expert (guru) of the soft contact lens industry. It all began, innocently enough, in 1969, with an assignment to find other uses for poly-hema, the unique material from which the soft contact lenses are made. A few years later, in the summer of 1972, having an intimate knowledge of the properties of this material, I was chosen to lead a study to determine the safety and efficacy of the Bausch & Lomb Soflens, the worlds first soft contact lens approved for marketing in the United States, earlier that year, in March. That assignment allowed me to interview nearly all of the original FDA investigators involved with testing the lens, and provided me with an in-depth knowledge of soft lens technology. Following that assignment, I wrote the first marketing paper on the potential of the soft lens industry, published by Arthur D. Little’s Decision Resources in September 1973 (1), followed by two others in succeeding years (2,3).

One thing led to another, and by the mid-1980's, I had completed more than 150 soft contact lens-related assignments, including being part of the acquisition teams that advised Johnson & Johnson, Ciba Geigy, and Schering-Plough in getting into the soft contact lens business.

I advised Johnson & Johnson in their acquisition of Frontier Contact Lenses, later re-named Vistakon; traveled to Germany to evaluate the soft lens technology of Titmus-Eurocon for Ciba Geigy, which became the basis for CibaVision (they later acquired the company itself); and assisted Schering-Plough in their acquisition of Wesley-Jessen, which it later sold to CibaVision.

My work in this area culminated in my participation, as an expert witness, in the trial in the Tax Court case of Bausch & Lomb v. the Commissioner of the IRS. This landmark case involved transfer pricing between B&L’s soft lens production plants in Rochester, NY and Waterford, Ireland, where B&L paid much reduced taxes. Dr. Irving Plotkin, a renowned microeconomist and expert in tax-related transfer pricing, and I, formed the Arthur D. Little team that worked with B&L’s outside tax attorneys, Baker & McKenzie, to support B&L’s position in the case.

My expert report and testimony, along with Dr. Plotkin’s expertise helped B&L’s attorneys win a formidable judgement – which lowered B&l’s tax payment for the tax years 1980-1982. (We estimated that based on the judgement that reduced B&L’s taxes from $20 million to about $5 million, we saved B&L $60 to $90 million in taxes over the succeeding six to eight years.)

A good deal of my expert report (4) (along with Dr. Plotkin’s) can be found online by following this link. (I recently discovered that the link is no longer active.)

In my report, “The Nature and Evolution of the Soft Contact Lens Industry in the United States”, I provided a history of the development of both the hard and soft contact lens industries, including the materials involved, the manufacturing techniques and costs, and marketing and licensing practices.

The trial took place over about a two-week span in August 1987 in the Tax Court in Wilmington, DE and the final decision was delivered about two years later in March 1989.

1. The Outlook for Soft Contact Lenses, Irving J. Arons, Arthur D. Little, Decision Resources, September 1973.

2. The Outlook for Soft Contact Lenses, Irving J. Arons, Arthur D. Little, Decision Resources, September 1975.

3. An Update on the Market for Soft Contact Lenses in the United States, Irving J. Arons, Arthur D. Little, Decision Resources, October 1977.

4. Expert Testimony of Irving J. Arons, Arthur D. Little, Inc., August 1987, in the matter of Bausch & Lomb v. Commissioner, United States Tax Court, Docket No. 3394-86

Menu - Part 3: The Third List of Publications for Potential Posting

Here are some more interesting items for the Journal:

The Nature and Evolution of the Soft Contact Lens Industry in the United States

Early in my career at Arthur D. Little, I became involved with the soft contact lens industry. By the mid-1980's, I had completed over 150 assignments in this field. This writeup summarizes some of the work done and links to my expert report in a landmark Tax Court case that tells the history of the contact lens industry.

Before I began concentrating on ophthalmic and medical lasers, I spent much of my time working in the Arthur D. Little Product Technology laboratories on a myriad of interesting client-sponsored cases (and other interesting pursuits). I have decided to place a few of the more interesting on my web Journal, under the title “ADL Chronicles”. Here are a few:

ADL Chronicles – The EPCON Plastic Pencil

One of my early lab assignments was to develop the materials for the all plastic pencil that we developed for the Empire Pencil Company, a subsidiary (then) of Hasbro Toys. We developed a material and a co-extrusion process that went into commercial production. We obtained two patents on the materials and process that was assigned to Hasbro.

ADL Chronicles – Spin-cast Eyeglass Frames

Another lab-based assignment was to develop an epoxy-based eyeglass frame for Universal Optical, similar to, but getting around the patents held by the Optyl Company. We decided to use a spin casting system and had to invent both a compatible material and process for making the frames. We succeeded in the development (including obtaining a patent), but the process never went into commercial production.

ADL Chronicles -- The Disposable "Motionless Mixer"

This was a unique assignment – to develop a delivery system for two-part adhesives that would not require mixing by the user. We settled on using a prior ADL invention, the motionless mixer, but had to find a vendor that could make it disposable, instead of very expensive as was the original mixer. We did, and this product went on to become a commercial success, although it was not patentable.

ADL Chronicles – An Improved Firefighter’s Glove

Our first assignment was for NIOSH (the National Institute for Occupational Safety and Health), to determine what the hazards were affecting the hands of firefighters during fighting fires. The followup assignment for NASA was to use that knowledge to develop a glove of space-age materials that would meet or exceed the criteria that we had uncovered in the first assignment.

We ended up developing (and patenting) several designs of improved firefighter’s gloves that were picked up and commercialized by glove manufacturers.

ADL Chronicles – An Erasable Ink Composition

In the early-1980's, the Gillette Corporation’s Papermate Division had developed and marketed an erasable ink pen. BIC, not wanting to be left out of the game, hired ADL to develop a composition for its use. And so we did, including obtaining a patent on our formulation.

ADL Chronicles – Of Silk Purses and Lead Balloons

And, one for fun. Following in Arthur Dehon Little’s tradition of his producing a “silk purse” from sows ears, the chemists and engineers of the Product Technology Section of ADL decided to hold a contest to see if we could produce a “lead balloon” that would fly! And so we did, and here’s the story behind the story.