BBI Contributing Editor

CHICAGO – The annual meeting of the American Academy of Ophthalmology (AAO; San Francisco), the largest gathering of eye physicians in the world, took place amidst brilliant fall weather of mid-October at the McCormick Place convention center. As in past years, a series of Subspecialty Day programs preceding the main meeting were held, focusing on a wide variety of topics such as glaucoma, neuro-ophthalmology, pediatric ophthalmology, uveitis, retina and refractive surgery. While the former four courses were only one day in length, the latter two were a full two days, primarily reflecting the rapidly changing technology landscape and the myriad disorders seen by those specialists.

It was just a decade ago that the first really safe and effective refractive surgery technology, using the excimer laser, was introduced into the U.S. The pace of technological innovation in the past 10 years has been formidable and today refractive specialists now have a wide array of technologies to offer their patients.

According to an article by Richard Lindstrom, MD, founder of Minnesota Eye Consultants (Minneapolis) and one of the most highly regarded ophthalmic surgeons in the world: “never before has ophthalmology had so many outstanding options for correcting refractive error. We are witnessing a dramatic improvement in visual performance and patient satisfaction.”

This fact became very evident to observers of the refractive surgery industry during a panel discussion on Saturday afternoon, when several of the world’s experts gathered to discuss and debate real patient cases and the best way for these patients to be treated. These physicians carefully considered the appropriate approach for both intraocular lens (IOL) refractive surgery and the corneal refractive surgery.

The fascinating aspect of these discussions, especially the IOL segment, was not only that there are significant choices now available to these physicians but that there was heated debate and outright disagreement in most cases as to what was the most appropriate approach to correct a refractive disorder.

The moderator for the Saturday afternoon sessions was Robert Osher, MD, a professor of ophthalmology at the University of Cincinnati School of Medicine, who kicked off the two sessions by commenting that “this is clearly the year of the IOL in refractive surgery.” Osher was referring to the recent introduction of the accommodative IOL Crystalens from Eyeonics (Aliso Viejo, California), the so-called pseudo-accomodative IOLs from Advanced Medical Optics (AMO; Santa Ana, California) and Alcon Laboratories (Fort Worth, Texas), and the phakic IOL Versisyse, also sold by AMO.

During one portion of the debate, one physician in the audience whispered to a nearby colleague that “two or three years ago, this type of debate could never have occurred,” because the choices were simply not there.

In the midst of these several new and existing, well-respected older technologies, it is important to not overlook the landmark decision that was reached by the Centers for Medicare & Medicaid Services (CMS; Baltimore) earlier this year. Following an intense lobbying effort by the cataract and refractive surgery companies, CMS agreed that it would cover the therapeutic portion (i.e., treatment of a cataract) of an IOL procedure and that the patient could choose to pay out of pocket for the refractive portion. That was clearly divergent from CMS’s past policy, which had treated a “plain vanilla” IOL solely as a therapeutic device, with an average reimbursement from CMS of about $100 per lens.

With this new decision, IOL manufacturers are now enjoying lucrative selling prices for these hybrid cataract/refractive lenses. The average selling price of these lenses from Alcon, AMO and Eyeonics is averaging about $850 per lens, which compares very favorably to the aforementioned average selling price of about $100.

Manufacturers are not the only beneficiaries of this decision; refractive surgeons, who already are extremely well-compensated for their toils, have experienced a surge in their incomes. Cataract surgery, which one physician recently described as his “charitable contribution” to society because of its far lower income generation relative to refractive surgery, has now become a lucrative endeavor, with procedural fees now vastly higher as the refractive component is factored in.

Lindstrom gave the final talk of the day, titled “Refractive Surgery Faces the Future,” He cited several technologies or surgical techniques that he predicted would become an important part of the refractive surgical landscape by 2010.

With the anticipated rapid market acceptance of multi-focal and accommodative IOLs, which can result in surgically induced astigmatism, Lindstrom predicted that astigmatic keratotomy, a surgical technique that can correct up to two diopters of astigmatism, would play an important role in the future.

Ivan Ossma-Gomez, MD, assistant professor of ophthalmology at Fundacion Oftalmologica de Santander (Santander, Colombia) discussed the Synchrony lens, which was designed by Visiogen (Irvine, California). This IOL features a novel, silicone dual optic system with a plus-powered lens anteriorly and a minus-powered lens posteriorly, joined by a spring. Accommodation is achieved when the two lenses move back and forth with the contractions of the ciliary body in the eye. Ossma-Gomez discussed a drawback of this lens, surgically induced astigmatism. Since these lenses were implanted in Europe, Visiogen has successfully developed a slick pre-loaded IOL injector system that will be used in its upcoming U.S. pivotal clinical trials.

Visiogen received its IDE to begin a pivotal trial in December 2004 but delayed the launch of the trial as it developed its pre-loaded injector system. Now that the injector, which was developed internally, has been perfected, the company will begin the trial. David Chang, MD, from Altos Eye Physicians (Los Altos, California) will be the medical monitor.

Buoyed by its solid clinical results and ongoing improvements in the technology, Lindstrom opined that “LASIK is an excellent procedure and it is here to stay.” Nevertheless, surface ablation technologies such as the long-established photo-refractive keratectomy (PRK) and relatively new EPI-LASIK will encroach on LASIK’s current market share. Whereas LASIK commanded a 95% share of the laser refractive market the past couple of years, according to Marketscope (Manchester, Missouri) LASIK’s share has dipped below 90% this year. Marketscope CEO Dave Harmon told The BBI Newsletter that he is expecting LASIK’s share to further slip to about 85% next year.

Lindstrom noted that small diameter intracorneal lens, which often are referred to as corneal inlays and onlays, will become a viable option for the correction of presbyopia for patients who otherwise have excellent vision. These so-called emmetropic (plano) presbyopes are attracted to intracorneal lenses because the procedure can be easily and safely removed.

Although not specifically mentioned by Lindstrom, two prominent companies in this category are two privately owned, venture capital-backed southern California companies, ReVision Optics (Lake Forest) and Acufocus (Irvine).

ReVision Optics has developed a multifocal lens made from a proprietary micro-porous, biocompatible hydrogel. It addresses the correction of emmetropic presbyopia, hyperopic presbyopia and moderate to severe hyperopia. The company, which recently changed its name from IntraLens Vision, completed its Phase II feasibility trial late last year and is now awaiting FDA approval to begin its pivotal trial.

This trial, which will be led by co-principal investigators Roger Steinert, MD, professor of ophthalmology and biomedical engineering at University of California Irvine and Stephen Slade, MD, Slade and Baker Vision Center (Houston), will enroll 300 hyperopic and presbyopic eyes. All patients are expected to be fully enrolled by the first half of 2007. A two-year follow-up, as mandated by the FDA, suggests that final domestic approval could come late in 2009.

The Acufocus lens features an ultra-thin, opaque, biocompatible corneal inlay device inserted under a flap in the corneal bed. Daniel Durrie, MD, of Durrie Vision (Overland Park, Kansas), who presented the Acufocus story, once described its device in layman’s terms as a “doughnut in the eye.” Durrie will be the company’s medical monitor for its upcoming U.S. clinical trial.

The design is based on a small-aperture optics principle that is not expected to interfere with the normal function of the lens so the patient’s distance vision will remain unaffected. This process allows the presbyopic patient to focus on objects that are within an arm’s length.

According to CEO Ed Peterson, outside the U.S. 145 eyes have received the lens to date, with extremely impressive results. Specifically, Peterson reported that the mean uncorrected visual acuity for this patient cohort is 20/20, with all patients enjoying J1 (i.e., superb) reading ability as well.

The excitement in the refractive surgical community has been impressive. Highly respected ophthalmologist Jack Holladay, MD, of Holladay LASIK Institute (Bellaire, Texas), after carefully examining this technology several months ago, said, “this is the most exciting concept I’ve yet seen for the treatment of presbyopia.”

Acufocus has filed for an IDE with the FDA and hopes to begin its pivotal, multi-center clinical trial in the U.S. in the first half of 2006. As in other refractive surgical devices, it is likely that the trial will involve 300 eyes, with a two-year follow-up.

Durrie, who will be the principal investigator, recently told BBI that this approach “has the potential to be the product we’ve all been looking for.” He will be joined in the clinical trial by several other well-known “who’s who” refractive surgeons. Without doubt, the results of this trial will be carefully watched and keenly anticipated.

Regarding accommodative IOLs, Lindstrom noted that while the current lenses will achieve excellent commercial success, these products should be viewed as “first generation.” Indeed, in spite of their limitations, these multi-focal IOLs are off to a tremendous start.

In the first issue of the EyeQ Report, published by Lachman Consulting (Walnut Creek, California), Michael Lachman, a former Wall Street analyst, estimated that about 90,000 presbyopia-correcting IOLs will be implanted globally in 2005, generating sales of about $75 million to $80 million. Moreover, with full-year FDA approvals for both ReSTOR and ReZoom and a full year with these lenses available to Medicare patients, Lachman predicted that sales could approach $200 million and implants could exceed 200,000.

Lindstrom predicted that within the next five years, IOLs would achieve “true accommodation,” generating at least four diopters or more of accommodation. Several privately financed, venture-capital backed companies are in hot pursuit of this Holy Grail. This list includes PowerVision (San Carlos, California), Nulens (Herzliya Pituach, Israel) and Medennium (Irvine).

Additionally, at least two public companies are in the race. AMO, through its acquisition earlier this year of Quest Vision Technologies (Tiburon, California), is working in this area with an interesting design, while vision care giant Bausch & Lomb (Rochester, New York), through its July 2003 licensing agreement with Faezeh Mona Sarfarazi, MD, is developing a single-piece molded silicone lens with a dual-optic design.

None of these companies has begun their human trials as of yet and are either in the prototype and animal testing stage. Given that the FDA requires a two-year follow-up, it is unlikely that any of these companies will be able to market in the U.S. until 2010.

However, their approach appears to be a significant advance over the other approaches, as their IOLs are being developed to mimic the action of the natural lens, which relaxes and constricts, based upon the need for distance or reading ability. In effect, the optic shape will be the key determinant to the optic’s power.

In a mid-2004 talk in the UK, Emanuel Rosen, MD, a well-known ophthalmologist from Manchester, UK, said that “truly accommodating IOLs will be those with actual accommodation achieved by change of the curvature of the lens.” He went on to say that the current generation of multifocal and “pseudoaccommodating” IOLs for presbyopia are only an interim solution. “Pseudoaccommodating” refers to the fact that accommodation occurs by changing the location of a fixed-power lens.

According to Louis (Skip) Nichamin, MD, of the Laurel Eye Clinic (Brookville, Pennsylvania) and a member of the PowerVision scientific advisory board, “there is no question in my mind that the future of accommodative IOLs is in shape change.”

Lindstrom noted that new technologies, still in the development stage, will positively impact the IOL market. He cited the Calhoun Vision (Pasadena, California) light adjustable lens (LAL), which has the unique potential to correct residual refractive error in all types of IOLs, including multi-focals and accommodative lenses.

The LAL is a foldable, three piece IOL with a proprietary, cross-linked photosensitive silicone polymer matrix, a homogeneously embedded photosensitive macromer and photo-initiator, which when exposed to a low-intensity beam of light from a digital light device, induces localized polymerization of the macromer. The light delivery device was developed by Carl Zeiss Meditec (Dublin, California). The exposure to light causes macromer diffusion to occur, which leads to a change in the lens shape and power. Effectively, this can correct refractive error in the lens.

At the refractive subspecialty day, Arturo Chayet, MD of the Codet Aris Laser Vision Institute Tijuana, Mexico) reported on the results of the first 16 patients treated by the LAL. All 16 patients were able to achieve a correction within 0.25 diopters of the intended outcome, prompting Chayet to say, “this new technology shows tremendous promise.” The company hopes to complete enrollment of a 30-patient trial, which will form the basis for its CE-mark application, in the second quarter of 2006. Calhoun Vision also hopes to receive FDA approval to initiate its pivotal trial in the U.S. by mid-year 2006.

Finally, Lindstrom said that he expects phakic IOLs to play a meaningful role for the correction of moderate-to-high myopia, especially when a multi-focal correction can be included. Phakic IOLs initially are addressing a relatively small market opportunity of patients with high myopia, which is generally defined as -6 diopters and higher. According to Lindstrom, patients with 6 diopters of myopia account for only 14% of the U.S. myopic population, with those with more than 10D accounting for just 2% of the population. However, it is well known that these patients account for a disproportionately high number of refractive surgeries. Marketscope’s data has shown that about 25% of these patients have had refractive surgery, compared to about 7% to 8% for moderate myopes and less than 5% for low myopes.

Thus far, just one phakic IOL, the Verisyse has received FDA approval, although STAAR Surgical (Monrovia, California), is very close to final FDA approval. Whereas the Verisyse is made of a hard plastic material and requires a large 6 mm incision, the STAAR lens, tradenamed Visian, can be implanted in a more conventional 3 mm incision.

Neither of these “first” generation of phakic IOLs provide multi-focality, and Lindstrom predicted that this feature will likely be incorporated in future lens designs.

Also at AAO, Refractec (Irvine, California) reported preliminary clinical results affirming the safety and efficacy of its NearVision CK (conductive keratoplasty) treatment for presbyopic patients with a history of LASIK surgery. NearVision CK is a quick (three-minute) treatment that uses radio waves, instead of a laser or a scalpel, to bring near vision back into focus without cutting or removing any tissue. NearVision CK is FDA-approved for the treatment of presbyopia and hyperopia, and Refractec is seeking expanded approval to improve near vision in post-LASIK patients.

The Phase III multicenter post-LASIK clinical trial will involve 150 patients. Preliminary results of the first 23 patients compiled one month after the treatment showed excellent safety (no flap complications or adverse events) and outstanding visual outcomes for the entire range of vision.

Also at the AAO meeting, Refractec reported the launch of an investigational device exemption study, recently approved by the FDA, of NearVision CK with LightTouch. The company is seeking supplemental premarket approval for LightTouch, a neutral-compression technique that it said delivers even more consistent, repeatable results.