BBI Contributing Editor

PHILADELPHIA, Pennsylvania — Writing in a recent issue of Ocular Surgery News, Dr. William Maloney of Vista, California, described the last 20 years as "the golden age of cataract surgery and ... [that] the consistently excellent refractive results of today's state-of-the-art cataract surgery exceeds even our recent expectations." As witnessed during this year's annual Symposium on Cataract, IOL and Refractive Surgery of the American Society of Cataract & Refractive Surgery (ASCRS; Reston, Virginia), held here last month, this trend appears to be moving forward very impressively.

Cataract surgery, the removal of a clouded natural crystalline lens and the subsequent implantation of an intraocular lens (IOL), is the most common surgical procedure reimbursed by Medicare. According to Marketscope (St. Louis, Missouri), which publishes a monthly report called Cataract Market Perspectives, about 2.7 million cataract procedures will be performed in the U.S. in 2002. The lion's share of these procedures occur in the aging Medicare cohort.

Enormous technological improvements over the past two decades, enabling the procedure to be performed quickly and minimally invasively, have made the procedure remarkably safe and effective. Nevertheless, problems still do occur, which has led to the development of a very new concept that could revolutionize the field. The specific problem is that intraocular lens implants, while providing dramatic patient benefit, often do not provide perfect vision. This is the result of several factors, including inaccurate pre-operative diagnostic information, pre- and post-op astigmatism, variable wound healing and movement or rotation in the IOL post-implant.

According to the American Academy of Ophthalmology's (AAO; San Francisco, California) National Eye care Outcomes Network (NEON) cataract surgery database survey of 7,626 patients operated on during 1996 and 1997, the mean absolute value of the difference between actual and target spherical correction was 0.8 diopters. Forty nine percent of the patients were within 0.5 diopters of target spherical correction, and another 29% were between 0.5 and 1.0 diopters of target spherical equivalent. Five percent of patients had an actual spherical equivalent of more than 1 diopter. Of the 5% of patients with over 1 diopter miss, data were not presented as to how many.

An incorrect intraocular lens power is the No. 1 reason for residual refractive error that in the worst and uncommon case may result in the need to explant the lens and, in less severe and far more common cases, results in the need for spectacle usage after the procedure. The AAO's NEON survey showed that 61% of all post-cataract patients required glasses.

Attendees at this year's ASCRS gathering heard about a new technology that could solve this dilemma and provide a dramatic leap forward in the success of cataract surgery. A private company, Calhoun Vision (Pasadena, California), is developing a process whereby an IOL can be adjusted non-invasively post-implantation to correct refractive IOL error.

The approach would work as follows. The surgeon would implant the Calhoun Vision proprietary IOL, called the Light Adjustable Lens (LAL), using standard cataract surgery techniques. After the eye has healed for a two-to-four-week period, the patient would return to have the lens customized to attain perfect vision. The surgeon would be able to precisely adjust the lens to the patient's specific needs and "tune" the lens to the appropriate power.

This technology is based upon a concept hypothesized by Dr. Daniel Schwartz, associate professor of ophthalmology at the University of California, San Francisco (San Francisco, California) and refined at the California Institute of Technology (CalTech; Pasadena, California). Schwartz, chairman of the board and a founder of Calhoun, thought that the curvature of an IOL could be customized using a laser or light source, while the CalTech scientists developed an ingenious solution to lens adjustability with a unique material and holographic technology.

The LAL is composed of a cross-linked photosensitive silicone polymer and a "guest" macromer, which when treated with the appropriate amount and wavelength of light polymerizes the macromer and changes the lens curvature, thereby adjusting the lens power. The lens power can be increased or decreased, depending on where the light is applied. At this juncture, therefore, myopia, hyperopia and astigmatism appear treatable.

The light source is an inexpensive device that delivers radiation in the near-UV range to adjust the IOL. These in vivo adjustments can be repeated several times, until the desired vision is achieved, and then the lens power can be locked in permanently .

Calhoun, privately financed with angel funding to date, has done extensive animal (rabbit) studies, demonstrating biocompatibility and safety of the material, predictable IOL power changes after irradiation and high optical quality. The company is preparing to submit an investigational device exemption application to the FDA and hopes to begin its U.S. human feasibility trial by August or September. Broader domestic trials could begin sometime in 2003, with potential final FDA marketing clearance possible in 2006 or 2007. The company said it intends to apply for a CE mark in Europe to enable it to launch commercially there in late 2003.

Before a standing-room-only audience at ASCRS, two separate papers were presented to explain this concept. Dr. Robert Maloney, co-founder of the Maloney-Seibel Vision Institute (Los Angeles, California) and one of Calhoun's founders, proclaimed that this new technology "will change the paradigm of intraocular lens implants." Maloney's sentiments were echoed by Dr. Nick Mamalis of the Moran Eye Center (Salt Lake City, Utah) that this is "truly revolutionary technology" that will make cataract surgery far better in the future.

Cataract surgery has advanced tremendously in the past, and the addition of the Calhoun Vision technology portends huge patient benefits. More immediately, however, apakic (post-cataract) patients may begin to benefit from so-called "accommodative" IOLs, which adjust or accommodate automatically in the eye to the patient's near, mid and far vision needs.

Traditional IOLs do not correct for near vision, and thus the patients require reading glasses.

Privately financed C & C Vision (Aliso Viejo, California) is leading this charge, having completed its U.S. enrollment for its Crystalens in November 2001 and now in a mandatory one-year follow-up phase before submitting its premarket approval application to the FDA.

Several papers presented at ASCRS showed that this foldable silicone lens is safe and effective in providing patients with abroad range of good vision, although some industry watchers question whether it provides enough improvement in reading and whether its benefits are enduring. Nonetheless, based on a possible FDA approval in late 2003, the Crystalens would be the first accommodative IOL to be commercially available in the U.S. It is currently being sold in Europe under CE mark approval.

Several other companies are also are working in this area, although they appear to be several years behind C & C Vision. They include HumanOptics AG (Erlangen, Germany), Quest Vision (Tiburon, California) and Visiogen (Irvine, California).

The HumanOptics device, called the Akkommodative ICU, is made with a hydrophilic acrylic material. To date, it has been implanted in several hundred eyes outside the U.S., but none domestically. According to Dr. Riccardo Neeuschuler of the Ospedale Fetebenefratelli (Rome), this lens is easy to implant, and is very effective, providing accommodation of between two and three diopters, which is about 85% of the targeted correction.

Privately funded Quest Vision is developing a foldable silicone accommodative lens that it believes fully replicates the mechanism and design of the human crystalline lens. Its work in this area began 15 years ago and therefore claims to have some significant patent protection. The company has recently completed two independent studies that have validated lens movement and is now proceeding toward human clinical trials. In a talk at ASCRS, founder Randy Woods, DO, said that the goal of the Quest Vision lens is to provide accommodation in the range of five to six diopters.

Another company that has entered this space is venture capital-backed Visiogen, which was formed over a year ago with the backing of two of the most venerable medical device venture capital firms, Three Arch Partners (Portola Valley, California) and Sprout Group (Menlo Park, California). Its approach to accommodation is unique, using a two-lens system to provide excellent vision in all fields. Animal trials to date have demonstrated proof of concept and Visiogen plans to initiate offshore trials in the next couple of months. The company hopes to begin U.S. trials for this product, which is called the Sybchrony Lens, in the second half of 2003.

Not quite as groundbreaking, but just as exciting to those who follow the fortunes of STAAR Surgical (Monrovia, California) is that the ASCRS meeting marked a brightening in the dark clouds that have hung over the company for the past few years. In recent times, sales stagnated due to aggressive competitive and pricing pressures, while product recalls, proxy fights, lawsuits and management turmoil have hampered profitability. New products and an experienced management team at the helm have changed the company's outlook.

The field of cataract and refractive surgery has long been characterized by high levels of innovation and rapid adoption. STAAR, which in the early 1980s pioneered the foldable IOL that made minimally invasive cataract surgery a standard of care in the 1990s, has long been regarded as leader in technology. In the recent past, however, it has lost its edge due to internal turmoil. The selection of David Bailey, a savvy veteran of the ophthalmic surgery market, as the firm's CEO some 18 months ago has brought newfound stability to the company and the promise of better financial fortunes.

At last month's ASCRS gathering, several physicians reported that their clinical experience with the STAAR Implantable Contact Lens (ICL) was very favorable and that the product would play an important role in serving the refractive surgery market. The ICL is a collagen co-polymer implant that is targeted to treat common refractive disorders such as myopia, hyperopia and astigmatism. It is folded and implanted in the posterior chamber behind the iris and in front of the natural crystalline lens, requiring only topical anesthesia on an outpatient setting.

Surgeons are very familiar with this implant technique and patients have been enjoying very rapid visual recovery, similar to laser refractive surgery. Indeed, at a STAAR-sponsored analyst meeting conducted during the ASCRS gathering, Dr. Stephen Slade, a well-known cataract and refractive surgeon from The Laser Center (Houston, Texas), noted that many of his ICL clinical trial patients experienced a "wow" factor of very rapid and dramatically enhanced vision following their ICL implant.

The ICL is now approved for sale in numerous countries worldwide, including the entire European Union, Korea, Canada, certain South American countries and South Africa. STAAR completed its Phase II pivotal trial in the U.S. almost three years ago, enrolling more than 500 patients with an average dioptric correction in the -10D range (i.e., high myopia). According to Dr. John Vukich, the company's medical monitor, who is based at the Dean Medical Center (Madison, Wisconsin), the ICL "demonstrates excellent safety and efficacy," with very high patient satisfaction. Predictability and stability of the refractive correction are both rated very high and there are few significant complications seen in this trial, which was conducted at 15 centers and under the auspices of 20 ophthalmic surgeons.

The FDA may mandate a full three-year follow-up, which would delay STAAR's final FDA submission until 4Q02. Final FDA marketing approval could come late in 2003, marking the first FDA-approved refractive IOL to enter the domestic market. It is difficult to predict the commercial market potential of the ICL, but based on an average U.S. selling price of $700 to $800 and a 10% penetration of the current 1.5 million-procedure domestic laser vision correction (LVC) market, the potential market easily exceeds $100 million.

STAAR's ICL and other refractive IOLs will likely initially be relegated to the high myopia market, which accounts for just 1% of the population having myopic refractive error, but where an estimated to be 10% to 15% of the total refractive surgery potential patients are derived. However, several physicians at ASCRS indicated that a significant number of hyperopic and astigmatic patients will also be prime candidates as clinical trials are completed and FDA approvals are received. Moreover, the ICL market also will include non-LVC candidates, such as patients with dry eye, thin or irregular corneas and other ocular abnormalities where a corneal incision would be ill-advised. According to Dr. Doug Koch, a noted cataract and refractive surgeon and chairman of the department of ophthalmology at the Baylor College of Medicine (Houston, Texas), "after [diagnostic] testing, I reject one-quarter to one-third of my patients who are seeking LASIK, due to various corneal pathologies."

STAAR also is moving forward with its plans to commercialize a toric (astigmatic) ICL. It said it hopes to initiate its U.S. trial in the fourth quarter of this year and, according to the company, patient enrollment of 125 patients is expected to be very rapid. Thus, STAAR hopes to submit a premarket approval application to the FDA in late 2003 or early 2004, based on an FDA agreement that it will need just 12 months of patient follow-up.

Other companies that are visible in this niche include Medennium (Irvine, California) and Ophtec USA (Boca Raton, Florida). The latter appears to be the next-closest competitor, having completed its patient enrollment in April 2001 and now in the FDA-mandated followup, which may also be for as long as three years. The required followup period will be determined at an Aug. 1-2 meeting of the FDA Ophthalmic Devices Advisory Panel. Papers presented at ASCRS indicate that this anterior chamber lens, called the Artisan, is both safe and effective in treating high myopia and astigmatism, but requires more follow-up for commercialization. Advanced Medical Optics (Irvine, California), a new firm being spun off from Allergan (also Irvine), has secured a an exclusive license for North America and Japan and a co-exclusive license for the rest of the world from Ophtec to develop its own brand of phakic IOLs based on the latter's technology.

Medennium also is in the midst of its pivotal U.S. trial with its posterior chamber Phakic Refractive Lens (PRL). The clinical results reported at ASCRS appear solid, but the company is unlikely to receive final FDA approval until 2006. It has granted the Ciba Vision (Duluth, Georgia) division of Novartis (Basel, Switzerland) a worldwide distribution license to sell the PRL. CE mark and other offshore approvals already have been received.

STAAR also is optimistic about its Aquaflow collagen glaucoma device, FDA-approved in July 2001. That device, used to perform a procedure called "non-penetrating deep sclerectomy," replaces several other glaucoma surgical procedures that appear less efficacious and are more risky. Dr. Stephen Bylsma, of the Shepard Eye Center (Santa Maria, California), who is the medical monitor and main champion of this product, said there is a huge need for this procedure in patients who are failing medical management. He said there is a groundswell of support for Aquaflow, as more ophthalmologists are trained and see the benefits and safety vs. conventional trabeculectomy. He did note, however, that the procedure has a learning curve and would benefit from improved surgical instruments.

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