ASCRS 2000: corneal inlays, onlays still in development

Issue: July 15, 2000

ByIrving J. Arons

More than 10,500 people attended this year’s annual meeting of the American Society of Cataract and Refractive Surgery (ASCRS) in Boston, including about 7,000 physicians and other medical personnel, along with about 3,500 exhibitors’ personnel representing about 300 companies. Meeting participants attended 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 also were presentations on treatments for glaucoma and retinal disease, including the newly approved Visudyne (verteporfin for injection; QLT Inc./CIBA Vision) therapy for halting classic age-related macular degeneration.

As usual, I concentrated on two areas: the latest developments in laser refractive surgery and 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 — that is, a better refraction — for performing laser in situ keratomileusis (LASIK). I conducted a survey of all the major U.S. and international laser companies to determine the specifics of their lasers and trackers, where available, and the diagnostic device(s) they intend to use to perform customized ablations. The survey results will be published in an upcoming issue of Ocular Surgery News.

In this article, I present some of the interesting new technologies on display, some of which are in clinical trials while others are just beginning to be developed.

Inlays, onlays, rings and things

In 1990, following that year’s ASCRS meeting, I wrote a column for another ophthalmic publication with the above title. I described some of the interesting approaches to correcting vision, from the mild renewed interest in radial keratotomy (RK), probably brought on by the then intense interest in photorefractive keratectomy (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 of shaping the cornea. Some of the advances under way 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 also were presentations about the possibility of injecting either a hydrogel or silicone material into a cleaned out capsule by means of 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, also from Allergan; 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 Corporation had developed a Fresnel hydrogel intracorneal lens. KeraVision intrastromal corneal rings were still in pre-clinical trials.

As for onlays, Chiron Ophthalmics and GE Medical Systems sponsored programs to place either hydrogel or collagen onlays on de-epithelialized corneas and have the epithelium grow back over the onlay to hold it in place. (Do not forget that there were no meaningful microkeratomes available at that time.) GE’s program was under way 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-epithelialization.

And then there was the injectable lens. Innovative Surgical Products (ISP), under the sponsorship of Allergan, 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, which would fill the capsule and provide accommodation. (Efforts at developing an injectable lens remain ongoing, but not by ISP or Allergan.)

Of all of these interesting technologies, only Intacs micro-thin prescription inserts (KeraVision Inc., Fremont, Calif.) ever made it into commercialization, having been recently approved this past year. However, similar devices and programs 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 and things revisited

Although not an intrastromal inlay, today’s implants include the collamer ICL, which is inserted in front of the natural lens, from STAAR Surgical for correcting high myopia (in phase 3 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 microprecision meniscus-shaped lenticle has an edge thickness of 10 µm and a center thickness of 30 µm to 50 µm for correcting hyperopia by steepening the cornea.

According to the company, the hydrogel mimics the stroma, with an identical refractive index to avoid optical aberrations and glare. Because of its microporosity and high water content, it 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 and making the procedure removable and replaceable similarly to the KeraVision Intacs.

To date, 11 animal eyes with up to 12 months follow-up and eight human eyes with up to 5 months follow-up have been implanted at three sites in three countries, with corrections varying from +2.25 D to +6.75 D. Clinical trials will be expanding over the next several months to new sites in Europe, the Middle East, South America and Canada.

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

Corneal surface

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 own, to reshape the corneal surface.

In the proposed technique, the gel is applied to the cornea’s surface, an applanator (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 then uses an excimer laser to ablate 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 the middle or end of this year. 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 corneal inserts or rings, I learned that KeraVision Inc. has plans to expand the range of correction of Intacs from -1 D to -3 D up to -4.5 D. A phase 3 clinical trial is ongoing to assess the performance of the 0.21 mm, 0.4 mm and 0.45 mm intrastromal corneal ring segments. There are also plans for compound myopia and/or astigmatic correction with shorter arc segments, hyperopia correction with the placement of 6 or 8 radial segments aligned similarly to RK incisions, and the treatment of keratoconus.

In a joint announcement at ASCRS, KeraVision and Clinical Research Statistics (CRS) LLP said an investigational device exemption is expected to be filed with the Food and Drug Administration (FDA) that would allow a physician- sponsored clinical trial to begin at CRS affiliated sites in the United States. CRS seeks to gain FDA approval to study six new indications for the Intacs technology, including Intacs for the treatment of keratoconus or corneal thinning, post LASIK glare and halos, post LASIK ectasia or corneal thinning, post LASIK undercorrection, post LASIK regression and an Intacs/LASIK combined procedure for correction of severe myopia.

Lasers

Other tidbits picked up by walking around the exhibit hall included a new laser method for treating hyperopia — the 1.9 µm diode laser from Rodenstock, owned by ProLaser Medical Systems; 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 J.T. Lin and SurgiLight are planning to do in treating presbyopia with an infrared laser system; and a little about how C&C Vision plans to develop its accommodating IOL.

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, by means of monovision, for presbyopia. According to Marguerite McDonald, MD, the treatment time totals about 3 minutes, and either eight or 16 spots are treated, each taking about 0.6 seconds once the hand-held probe is positioned and inserted into the cornea. About 400 patients have been treated to date, ranging from +1 D to +4 D.

The Rodenstock DTK system (diode laser thermal keratoplasty), produced by ProLaser Medical Systems, also uses a hand-held contact probe that focuses the laser’s energy into the stroma (without penetrating the cornea). U.S. clinical trials are expected to begin shortly. There are more than 20 Rodenstock 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.

Innovations

An interesting innovation Sunrise hopes to be able to have in the future is Internet connectivity. This allows the company to perform per procedure billing, but also allows collection of patient treatment and outcomes data. As the laser user adds in the preop and postop data from each patient, the compiled database 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 an innovative way of compressing the learning curve.

IntraLase has made considerable progress in developing its femtosecond laser, now called the Pulsion FS, with recent 510(k) FDA approval for use as a laser microkeratome. A planar cut takes about 1 minute to accomplish, and the company plans to decrease that time. The only problem, at least as seen in the demonstration video, is that the flap (or lenticle, when the system is 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 for commercial introduction at this year’s American Academy of Ophthalmology meeting, is creating the channels for Intacs insertion. Currently, creation of a removable intrastromal lenticle takes between 2 and 2.5 minutes, compared with 20 to 40 se-conds for excimer laser ablation (after flap formation). The laser will be sold on a per procedure basis when it becomes available.

It was not easy to understand the presentation in which J.T. Lin of SurgiLight attempted to describe what his company was trying to do to correct presbyopia. All that could be determined was that the company was conducting trials in Venezuela using its IR 3000 laser to ablate 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. The Venezuelan physicians were following the similar protocol that the company submitted to New York Ear and Eye Hospital (NYEE). The first group of 15 cases with 6 months follow-up was reported at the ISRS meeting.

Last but not least, Bill Link, the former head of Chiron Vision before it was sold to Bausch & Lomb, now running a venture fund (Versant Ventures) for ophthalmic projects, 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. During reading, the ciliary muscles can “push” the central optics forward to provide accommodation. More than 100 lenses have been implanted to date, with good results.

For Your Information:

Irving J. Arons is managing director of Spectrum Consulting with offices at 4 Harvard St., Peabody, MA 01960; phone and fax: (978) 531-0939; e-mail: iarons@erols.com. Mr. Arons has no direct financial interest in any of the products mentioned in this article, nor is he a paid consultant for any companies mentioned.