Whats ahead in 2010
New IOLs on the horizon

With two accommodating IOLs likely to be approved within the next 12 months, the premium market is again exciting

Synchrony lens Source: Abbott Medical Optics

Calhoun Vision's Light Adjustable Lens after implantation Source: Calhoun Vision

With a little bit of luck, 2010 might be the year of multiple premium lens approvals. Two lenses—Lxenstec’s Tetraflex (St. Petersburg, Fla.) and Visiogen’s Synchrony (formerly Irvine, Calif., now part of Abbott Medical Optics, Santa Ana, Calif.)—are the first accommodating lenses to be submitted for regulatory approval since the Crystalens (Bausch & Lomb, Rochester, N.Y.). Other premium lenses, including Calhoun Vision’s Light Adjustable Lens (Pasadena, Calif.), the NuLens (NuLens, Herzeliya, Israel), PixelOptics’ presbyopia-correcting lens (Roanoke, Va.), Imperial Medical Technologies’ presbyopia-correcting lenses (Cartersville, Ga.), and Presbia’s Flexivue (Hollywood, Calif.), are moving swiftly along towards late stage development. Couple these developments with the announcement earlier this year by Abbott Laboratories of its acquisition of Visiogen and last year’s eyeonics purchase by Bausch & Lomb, and the premium lens market could be on the precipice of an entire new paradigm.
EyeWorld asked leading cataract surgeons for their opinions; here’s what they had to say.

Visiogen’s Synchrony lens

The Synchrony lens is a foldable single piece, all-silicone IOL that has two separate optics connected by spring-like struts, which keep the optics separated, said David F. Chang, M.D., clinical professor of ophthalmology, University of California, San Francisco, and medical monitor for the U.S. studies.
“The rear optic is a minus lens, whose power is varied in order to produce the desired overall net IOL power,” he said. “In the U.S. trial, we used the first generation of a pre-loaded injector that allowed me to implant all of the IOLs through a temporal clear corneal incision under topical anesthesia.”
While the lens can be implanted through a small incision, the incision size needs to be about 3.75 mm, said Stephen S. Lane, M.D., clinical professor of ophthalmology, University of Minnesota, Minneapolis, as well as one of the U.S. investigators.
“We’ll probably be able to go through smaller incisions with advances in the cartridge and injection system that will continue to evolve,” he said. “We won’t get down to a 2.4 or 2.2, but anyone who looks at the lens will know why. There is no change in my surgical technique” during lens implantation.
It’s critical to release the lens slowly, allowing the anterior optic to come out under its own steam, said Mark Packer, M.D., clinical associate professor of ophthalmology, Casey Eye Institute, Oregon Health & Science University, Portland, Ore.
“The incision size is about 3.8 mm, but most of mine were 3.9 or 4.0 after implantation,” he said. “I found it easier to have a little bigger incision and not struggle with insertion.”
Others say that because the lens necessitates a change in incision size creation technique and manipulation of the lens to get it in the right space, “it will be challenging to get wide acceptance of the lens once it’s approved,” said Sanjay N. Rao, M.D., director, Cornea and Refractive Surgery, Lakeside Eye Clinic, Chicago. However, Dr. Rao also said the intermediate, distance, and near performance of the lens “is much more consistent from patient to patient when compared to some of the other premium technologies.” The Synchrony “requires excellent surgical technique and a perfect capsulorhexis,” said said I. Howard Fine, M.D., clinical professor, Casey Eye Institute, Oregon Health & Science University, Portland, Ore. The injector “is an ingenious design made by a toy maker,” he said. “In our practice, we’ve had good results and a good amplitude of accommodation.”
Results from various studies outside the U.S. “show movement of the lens inside the eye. This is a truly accommodating IOL,” Dr. Lane said.
Although commenting on specific results from the U.S. studies is not allowed while the lens is under investigation, Dr. Chang said studies outside the U.S. “show excellent subjective and objective accommodation. Specifically, there are two separate objective tests—lens movement on UBM and refractive change via wavefront aberrometry—that show good correlation with the subjective measures of accommodation. As with other accommodative IOLs, not every patient will get the same result, but the clinical data that has been reported is certainly very exciting and correlates with my own personal experience.”
Douglas D. Koch, M.D., professor and the Allen, Mosbacher, and Law Chair in Ophthalmology, Cullen Eye Institute, Baylor College of Medicine, Houston, is also impressed with the results of his study patients. “Everyone had good corrected intermediate vision, and most have good near vision as well,” he said. “Quality of vision seems excellent. We had a few patients who were a little off in IOL calculations, as one might expect with this type of IOL design. However, many were 20/20 uncorrected and I have not had to perform any LASIK/PRK enhancements on my 10 patients.”
He suggested surgeons may want to insert the Synchrony along the steep meridian to manage astigmatism, and “be a little cautious with the posterior capsulotomy.” There is very little PCO with this lens—only 1 in 10 for him at two years postoperatively and not even a hint of it in the other nine eyes.
A new technique of working making the posterior capsulotomy small and in a spiral pattern seems to be effective in preventing the rare occurrence of IOL dislocation, Dr. Koch said.
In the initial postop period, most patients will have signs of early myopia, Dr. Packer said. “The reason is that when the lens is in the bag, the capsule is still very elastic and open, so the optics are further apart. There’s a process by which the capsule shrinks some—not as much as with a three-piece lens—and by about three months we’ve got accurate final distance refraction.” In his study patients, those that were immediately myopic ended up plano at the three-month follow-up, he added.
Additional surgical pearls

Like any new device or technique, “the Synchrony has its own set of challenges,” Dr. Lane said. Among them: the lens is large and the injection system is novel. He recommends using a bimanual technique.
“The injector greatly eases the ability to consistently and predictably place the lens where you want it,” he said. “With this lens, you really have to make a circular and absolutely central capsulorhexis.” The capsulorhexis has to be around 5 mm or less, Dr. Koch said, because the anterior optic needs to be completely covered. If the capsulorhexis is too big, the lens will not work correctly and if it’s too small, it will be impossible to insert the lens properly, Dr. Packer said. “The other thing we’ve done is to aspirate the lens epithelial cells under the posterior capsule and that seems to have preserve a very clean, very quiet eye,” he said. For those unfamiliar with the lens, Dr. Koch said the lens unfurls in waves—first the posterior optic and then the anterior optic. The larger incision size will create more surgically-induced astigmatism, but “using a peripheral clear corneal incision is still the way to go,” Dr. Packer said. The U.S. studies excluded patients with more than 1D of astigmatism, but Dr. Packer believes once the lens is approved and surgeons begin using it in clinical practice, “I think we’ll see higher enhancement rates because of the astigmatism. I may change my pricing model based on that assumption.”
Dr. Fine said a potential hurdle with the lens is that “you can’t predict the bag size, so spherical equivalent is a little unpredictable postoperatively. Different bag sizes will generate different refractions.”
Dr. Packer said the initial cataract extraction is “no different” from standard biaxial surgery; the difference in surgical technique begins with the I/A. “The bag has to be completely clean,” he stressed. “That’s virtually impossible to achieve with a single incision. I think the best way is performing bimanual I/A.”
During the lens implantation itself, the posterior optic will emerge first, Dr. Packer said. “There is a tendency for the optics to get tangled or torqued if the posterior portion of the lens is not placed first. It’s critical to release it slowly and then let the anterior optic come out under its own steam,” he said. Dr. Packer—who implanted the second patient enrolled in the U.S. study about four years ago—said if the lens is implanted properly, the capsule remains “remarkably clear, even after long-term follow-up.” He theorized the way the lens fills the bag and keeps it open, minimizing contact with the IOL and allowing the aqueous to circlulate may reduce lens epithelial cell metaplasia. Outside the U.S., studies of the lens have shown no increased dysphotopsia, no higher order aberrations, no unwanted side effects with longer-term follow-up, Dr. Packer added. Along with Dr. Lane, Dr. Packer also recommends creating a small capsulotomy and “using the spiral-out technique. If that protocol is followed, there’s no chance for a dislocation.”
Lenstec’s Tetraflex lens

The Tetraflex is “very much like the Crystalens in its design and anticipated mode of action,” Dr. Fine said. “The lens itself is easier to implant than the Synchrony will be,” said Dr. Rao. “There won’t be a lot of change in implantation technique. There is still an inherent unpredictability in terms of outcome. It’s an accommodating lens and we’re relying on patient’s muscles to create the near vision effect. The problem is that it will work well in some patients, and may not in others. At this point, we cannot accurately predict who will do well with this lens.” Whereas the Crystalens is silicone, the Tetraflex is an acrylic lens, said Carlos Buznego, M.D., Center for Excellence in Eye Care, Miami, and voluntary assistant professor of ophthalmology at University of Miami’s Bascom Palmer Eye Institute. The Tetraflex is also hydrophilic, and has a little bit of a unique appearance with closed loop haptics, Dr. Buznego said. The lens itself can be implanted through a sub-2 mm incision, said Jim Simms, vice president of refractive products, Lenstec. Additionally, the lens has a high water content HEMA material, with a lower index of refraction than the hydrophobic lenses, said John Clough, president and chief executive officer, Lenstec. “The material is tremendously biocompatible,” he said. “We’ve got quiet eyes within a couple of hours of implantation. In a substudy where the Tetraflex was directly compared with the crystalens 5-0, “the lens did very well against both the crystalens and the standard monofocal,” Mr. Simms said. Dr. Buznego said “overall the patients we’ve enrolled achieved some level of spectacle independence. Some still use spectacles, but there was a definite significant improvement in reading speed and functional reading speed.”
The MNRead functional reading test was performed as a substudy at one year post-op in all Tetraflex patients presenting at four of the 12 investigative sites. As the study progressed, testing was added at six months and two years post-op in the Tetraflex group to determine stability of reading ability over time. Dr. Buznego said there was a statistically significant increase in reading speed for patients implanted with the Tetraflex; at 20/40 those in the control group read an average 26 words per minute (wpm) compared with 63 wpm in the Tetraflex group. Only 6% of the control group could read 80 wpm at a 20/40 print size, compared with 41% of the Tetraflex patients. “In my anecdotal data—all my patients had good reading acuity. The overall feeling was the level of spectacle independence was better than the monofocal IOLs. The Tetraflex seems to deliver similar or better results than the Crystalens,” Dr. Buznego said.
During the U.S. studies, patients with more than 1D of astigmatism were excluded, but there was “nothing new or dramatically different in the surgical technique,” Dr. Buznego said. Unlike the Crystalens, however, the Tetraflex is anteriorly vaulted, he said.
“When we’re inserting the Crystalens, we make sure the optic junctions vault posteriorly,” he said. “With this lens, my experience has been that it goes in through a small incision, and the actual placement is not very different from a clear corneal approach.
The lens goes through a lens shooter that can deliver it directly into the capsular bag. Once you’ve confirmed the lens is vaulted anteriorly, you’re done. This lens never has a tendency to vault posteriorly. From a surgeon’s perspective, it’s a really low-stress, low-effort insertion.”

The overall market

As these lenses come to market, “they’ll build more and more excitement of the overall market. Each year we’ve seen wonderful new advances,” Dr. Koch said. “We’re now seeing these coming to market at an accelerated pace, and patients have a lot of interesting choices. Surgeons will have to be savvy about how all these lenses work, but it’s a fun time to be in ophthalmology,” he said. The newer multifocal lenses “seem to give better distance and intermediate vision than what we’ve been seeing,” Dr. Rao said. Premium lenses control about 6% to 7% of the overall IOL market, he said. “What will happen is that entrance of some other lenses may not immediately impact the market share of established brands, but it will continue to drive the overall use of premium IOLs,” he said.
Of the lenses in earlier stage development, Dr. Rao believes the Light Adjustable Lens will have the biggest impact, “but it’s also the most significant in terms of capital outlay.” (For more on the Light Adjustable Lens, see sidebar).
The Synchrony can give patients a greater amplitude of accommodation than the crystalens, and surgeons should be able to have greater predictability with outcomes, Dr. Lane said. “The Synchrony has no vaulting; the lenses come together or move apart to create distance, near, and intermediate vision,” he said. The amount of lens movement will determine the amount of accommodation, “so some patients will have terrific vision, and others will not.”
At six months, 40% of multifocal recipients notice halos; 10% of those patients will find the aberrations bothersome, Dr. Packer said. After a year, only a few percent are still bothered by the aberrations. “Monofocal lenses result in about 5% who notice halos,” he said. “Our results with the Synchrony are much more like the monofocal than the multifocal.”
Dr. Chang said the distinct advantage of the Synchrony lens is that its dual optic design “maximizes the dioptric power of the moving lens. I have had extensive experience with Crystalens HD and its predecessors, and I am very encouraged by how my own Synchrony patients compare.”
The more lenses are available, the more the overall market will continue to grow, Dr. Buznego said. “These new technologies may have fewer ‘warts’ on them than current iterations. We’ll be able to better adapt and choose right lens for the right patients, although we may be premature to think we’ll have one right lens for everyone.”
Editor’s note: Dr. Chang is the medical monitor for the Synchrony (now Abbott Medical Optics, Santa Ana, Calif.) U.S. clinical trial and has financial interests with Abbott Medical Optics (AMO, Santa Ana, Calif.), Alcon (Fort Worth, Texas), and Calhoun Vision (Pasadena, Calif.). Dr. Lane has financial interests with Visiogen, but holds no proprietary interest in the lens itself. Dr. Packer has financial interests with AMO and Visiogen. Drs. Rao and Fine have no financial interests related to their comments. Dr. Koch has financial interests with Visiogen and Alcon. Dr. Buznego has financial interests with Alcon, Allergan (Irvine, Calif.), and Lenstec (St. Petersburg, Fla.). Dr. Price has financial interests with Calhoun Vision (Pasadena, Calif.).

Contact information

Buznego: 305-598-2020, cbuz@comcast.net
Chang: 650-948-9123, dceye@earthlink.net
Fine: 541-687-2110, hfine@finemd.com
Koch: 713-798-6443, dkoch@bcm.edu
Lane: 651-275-3000, sslane@associatedeyecare.com
Packer: 541-687-2110, mpacker@finemd.com
Price: 317-814-2823, fprice@pricevisiongroup.net
Rao: 312-553-1818, sanjayrao@pol.net