Sometimes it seems as if information on cutting-edge, unapproved intraocular lenses comes in dribs and drabs: a poster here, a podium presentation there, maybe an occasional journal article. It's hard to feel up-to-date. This article aims to change that. To help you round out your knowledge of IOLs in the pipeline, here's a look at the newest lenses, running the gamut from those on the cusp of approval to a couple that are just entering animal trials.
Pseudoaccommodation Roundup
Three lenses that have garnered a lot of interest are Alcon's ReSTOR, and AMO's ReZoom and Tecnis Multifocal, each aimed at providing patients with a usable amount of postop reading vision.
• Alcon's ReSTOR. The ReSTOR lens is designed on the principle of diffraction, or the ability to bend light by passing it through sharp edges.
The lens has 16 rings distributed over its central 3.6 mm that decrease in height toward the periphery. The central ring height is 1.3 µm, while the smallest is 0.4 µm. And, as they decrease in height, they are spaced closer together. So, the central part has more prominent rings that are farther away from each other, but the periphery of the 3.6 mm area has rings that are smaller and closer together. Each ring puts two things in focus, one at near and one at distance, and the brain chooses between them.
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| The Tecnis Multifocal IOL combines asphericity with a diffractive effect. |
In the U.S. Food and Drug Administration trial of the ReSTOR, researchers presented data from 578 implantations both here and in Europe, using monofocal IOLs as controls. Though the monofocal lenses gave slightly better distance vision (71 percent saw 20/20 or better vs. 63 percent of the ReSTOR eyes), ReSTOR researcher James Davison, MD, of Marshalltown, Iowa, says it's better to focus on the combination of distance and near uncorrected vision, or what he calls "functional vision." In this category, 84 percent of the ReSTOR patients could see both 20/25 at distance and J2 (20/30) at near, versus just 23 percent of the monofocal patients.
There's the possibility that intermediate vision is somewhat penalized with the ReSTOR, however. On one side of the issue, Dr. Davison says that there's actually an improvement in intermediate vision with the lens. "When graphed on a line, the ReSTOR actually has two humps of best vision, at near and at distance, while the monofocal lens has just one, at distance," he says. (See Figure 1) "And, because of this, the vision in the middle, the intermediate vision, gets better as it approaches the second hump while the vision from a monofocal lens continues to drop off."
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| Figure 1. The ReStor has two points of sharp focus, far and near, while the monofocal lens is designed for distance acuity, as shown by the peaks of the graphs. Intermediate distances are between the two humps, in inches. |
However, Richard Packard, MD, of HRH Princess Christian's Hospital in Berkshire, England, in a paper presented at the 2004 meeting of the American Society of Cataract and Refractive Surgery, reported his ReSTOR patients have to make visual compromises at the 60-cm intermediate range. While distance and near came in at around 20/20 to 20/25 for the most part on defocus curves for the 30 patients in whom he's implanted ReSTOR lenses, Dr. Packard reported that intermediate vision averages around 20/40. Three of his patients have to wear -1 D spectacles for intermediate work to negate the near add of the ReSTOR. He did note, however, that all of the patients, save one, are happy with their results. That one unhappy patient has a bit of macular degeneration that's causing decreased vision.
In the U.S. study, there was a 24-percent chance of moderate to severe haloes at night with the ReSTOR, so Dr. Davison says patients should be made aware of this possibility beforehand, once the lens achieves widespread use.
"If you're interviewing a prospective candidate who says, 'Haloes at night? I couldn't possibly live with that,' that wouldn't be a good person to implant the lens in." However, he notes that, of the 31 cases he performed, only three people complained of haloes. Of these, the two who complained the most stopped seeing them after a year, and the third still sees them, but says his newfound ability to see things up close makes up for seeing tiny rings when driving at night.
The target for ReSTOR approval is the first quarter of 2005. "I have hundreds of people waiting," says Dr. Davison.
• AMO's Tecnis Multifocal and the ReZoom. Berlin's Dr. Tetz says that the ReZoom lens is based on AMO's former multifocal, the Array, a refractive IOL, with slightly shifted zones of vision. "They moved the outer zones farther into the periphery to make the inner zones more effective," he says. There are different zones, for near, distance and intermediate, that are created by distributing the light at different foci. The lens has a 6-mm acrylic optic with OptiEdge technology, which is designed to minimize dysphotopsia.
The Tecnis MF uses the aspheric Tecnis design as its base, then adds rings based on a diffraction principle similar to that in the ReSTOR. "It gives you a near and a distant focus, each of which is very distinct," explains Dr. Tetz. "Since the rings start very close to the center and then continue out toward the periphery, usually with increasing distance between the rings, you get an effect that's not as pupil-dependent as a refractive lens. So, even in a smaller pupil, you still have a couple of diffractive rings and the lens can still perform."
He says there seems to be a limit to the amount of near addition that can be incorporated into either a refractive or diffractive system. "The refractive lenses, such as the Array and ReZoom, usually have 3.5 D on the lens level, about 2.8 D on the corneal plane, and about 2.4 D on the spectacle plane, which is somewhat less than the 3 D near addition at the spectacle plane that some patients seem to need," he says. "Now, the diffractive lenses, such as the ReSTOR and the Tecnis MF, have 4 D on the IOL plane, which is equivalent to 3 D at the spectacle plane, so both have a better near focus. That way, even if you are a little off on the final refraction, by maybe 0.25 D or even 0.5 D, they still work quite efficiently. However, for optimal performance of all multifocal IOLs, postop emmetropia is a main goal."
He says his early results with the Tecnis MF, gathered over the past year, have been good in hyperopes, because their corneas seem to be closer to the average corneal asphericity that's put into the design of the lens. He says, conversely, initial results may suggest that the ReSTOR performs a little better in myopes.
As for optical aberrations, Dr. Tetz says, "Every lens with more than one focus will have some glare or halo effects; it's as simple as that, because there is one image laid over another." He says that, with the Tecnis MF, it seems that if the patient is "a Tecnis eye with a Tecnis cornea"—meaning it fits into the "typical" corneal shape Pharmacia originally used to design the asphericity of the lens—then the patient isn't affected that much by unwanted light effects. He says he won't implant it in patients who drive at night for a living, or in pilots, however, because he thinks "there are simply limitations with people who have to deal with artificial lights with large pupil sizes."
The U.S. FDA clinical study of the Tecnis MF was due to begin last month. When and if it's approved, it will be implanted through a 2.8-mm incision using the AMO unfolder.
Bimanual-friendly Lenses
Companies and researchers are also learning more about IOLs designed to go through sub-2-mm incisions for so-called bimanual, or micro, phacoemulsification.
• The Advanced Vision Science Lens. AVS actually has two lens designs coming down the pike. The first to be approved will be a monofocal, three-piece lens made out of the company's new, proprietary hydrophobic acrylic material. It's implanted through a 3.2-mm incision. Eugene, Ore., surgeon Mark Packer, who has implanted 10 of the lenses in a U.S. clinical trial, says this initial approval won't be the groundbreaking one. Rather it will be the subsequent approval of the second, modified injectable version of the lens that should cause a stir, since it will go through a 1.5-mm incision. He says that the company hopes that once the standard lens is approved in early 2006 or so, it will be easier to get the modified micro-incision version approved soon thereafter.
"The new material is good for micro-incision implantation because it can be lathe-cut and is extremely resilient in terms of maintaining its conformation," explains Dr. Packer. "So, it can be rolled tightly, inserted through a sub-1.5-mm incision, and then unfold and maintain its shape in the bag. Also, it should have enough resilience to withstand the constrictive forces of the capsule as it fibroses, which is going to be very important for some of these new micro-incision lenses." The company is in the follow-up phase of 300 patients, and Dr. Packer estimates it will be about nine months before it submits its PMA to the FDA for the standard lens.
• ThinOptx ThinLens. This is a hydrophilic acrylic lens that's between 350 and 500-µm thick at the optic (between half and a third the thickness of a conventional IOL) andm 100-µm thick at the haptic. Since it's very thin, it can be rolled tightly into an injector and put through an incision of around 1.5 mm. The surgeon inserts the lens into the anterior chamber, where it unrolls. Then, he floats it down into the capsular bag.
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| The ThinLens can be rolled tightly and inserted through a 1.5-mm wound. Photo: Jorge Alio, MD |
He says the other benefit of having a lens that goes through such a small wound is that the procedure induces less astigmatism, and uses less total phaco power and effective phaco time than conventional cataract surgery.
The main complications in a small, 50-patient study of Dr. Alio's earlier cases were inverted implantations (4 percent) and posterior capsular opacification (4 percent). He says the frequency of these complications has decreased as he's become more skilled in ThinLens implantation, and that they're mainly technique-oriented.
According to ThinOptx, the lens is about two years away from arriving in the United States.
Lenses That Accommodate?
In an attempt to restore accommodation, some lens makers are avoiding the multifocal route and trying to restore the eye's natural accommodative back-and-forth action as described by German scientist Hermann von Helmholtz.
• Visiogen's Synchrony. The Synchrony uses a novel dual-optic system, with a plus-powered silicone lens anteriorly and a minus-powered lens posteriorly, joined by spring haptics. When the two lenses are close together the eye is set for distance vision. Then, as the ciliary body contracts, this takes tension off of the zonules, the capsular bag relaxes and the lenses are allowed to spring apart by 0.5 to 1 mm. During this separation, the front lens moves forward, changing the eye's focus to near. Stephen McLeod, MD, vice chair of ophthalmology at the University of California-San Francisco and a Visiogen consultant, says the natural tone of the capsular bag keeps the lenses together, storing energy in the spring that "wants to push the lenses apart."
Currently, the front lenses in the Synchrony are in the 30 to 35 D range and the back ones are from -8 to -12 D. The front optic is 5.5 mm in diameter and the back is 6 mm.
In a small study of 25 Synchrony patients performed by Ivan Ossma, MD, of Bucaramanga, Colombia, the system appears to improve near vision. Of 16 patients available for a six-month follow-up, uncorrected vision went from a mean of 20/40 preop to 20/25 after surgery. Dr. McLeod says, however, that with an accommodating lens, "What you're most concerned about is the patients' best distance corrected near visual acuity, because you want to know that, when you've taken all the myopia out of the system, that they're still able to accommodate at near distances." By this measure, even with distance correction in place, the patients still had a mean best distance corrected near vision of about 20/25. "We've also demonstrated proof of principle by showing lens movement under pharmacologic stimulation with B-scan ultrasound," offers Dr. McLeod.
Dr. McLeod says the sutures required to safely close the relatively large 4.5-mm incision that the lens goes through result in postop astigmatism, but that this induced cylinder gradually decreases with time. In Dr. Ossma's study, the postop cylinder is 1 D at one month, 0.75 D at three and 0.52 at six. To help remedy this, the company is developing an injector that it hopes will enable surgeons to implant the lens through smaller incisions.
One eye in Dr. Ossma's study has had posterior capsule opacification, and one required explantation for a capsulorhexis that was too large. There haven't been any cases of interlenticular opacification thus far.
The FDA approved the Investigative Device Exemption for the Synchrony in mid-December, and the company hopes to begin trials in 2005, during which time it will also introduce the injector in trials outside the United States.
• Medennium's SmartIOL. This is another accommodative lens that's farther down the road from approval. According to Stephen Zhou, PhD, vice president of research and development for Medennium (Irvine, Calif.) the lens is made of a "smart" material that has a phase transfer temperature slightly lower than that of the human body. When in it's in conditions below this temperature, the material is a rigid, solid rod. At body temperature, however, it transforms into a soft, gelatinous, biconvex lens with a consistency Mr. Zhou describes as similar to a young, human crystalline lens. "The whole design principle is built on the softness of the IOL and its similarity to the human crystalline lens," he says. "So, since the lens is soft, the zonules can stretch and compress it, possibly enabling the eye to see in the distance or at near." The lens hasn't been used in animals yet, only cadaver eyes.
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| The Medennium SmartIOL shows movement in a simulated capsule (top), and fills the bag in a model eye out to 9.5 mm (bottom). |
The researchers simulate accommodative effort in cadaver eyes by affixing the model eye to an 11-mm rubber ring. They then slightly stretch the rubber ring to see how the lens changes shape. They also have a synthetic 0.1-mm silicone lens capsule in the lab into which they can inject the lens and then stretch in order to observe how the stretching force is transmitted to the lens and changes its shape.
Mr. Zhou hopes the lens, which will fill the bag to a full 9.5 mm, will avoid problems with edge glare, since the pupil won't dilate as wide as 9.5 mm.
Medennium is also working on U.S. clinical trials with a hydrophobic acrylic lens, the Matrix Acrylic IOL, which has already been marketed in Europe and Asia for three years. Its purported benefit isn't accommodation; instead, it's the haptic material, polyvinylidene fluoride (PVDF), that the company thinks will make a splash. PVDF's properties include shape memory and durability.
"The PVDF haptics are unbreakable," says Mr. Zhou. "They're only able to be fractured by cutting with scissors. Because of this, we're developing an injector and cartridge system that we hope will enable us to squeeze the lens into an injector, and then implant it through a 2.2 to 2.4-mm incision. We're still in the testing stage, working out some of the design bugs. It now goes through a 3-mm incision with forceps."
The Matrix Acrylic U.S. study needs to enroll 200 more patients, and it will be about three more years before it will be ready for approval in the United States, Mr. Zhou estimates.
Other Trials
• The Light Adjustable Lens. This lens may enable surgeons to adjust its power even after its been implanted, possibly making postop "surprises" a thing of the past.
The lens, from Calhoun Vision, is a silicone matrix full of unpolymerized silicone macromers that are connected to photosensitive molecules.
The macromers are only partially polymerized, allowing the lens's power to be adjusted in the eye with a 365-nm wavelength light. This polymerizes the unpolymerized macromers in a certain configuration based on what the surgeon needs to correct a patient's refractive error. To generate a specific change in power, the light passes through a special filter that shapes it into the right spatial intensity distribution. Wherever the light strikes the lens, it increases the thickness of the silicone in that area. For example, one distribution pattern might put more light in the periphery of the lens to cause a relative flattening of the center, which could correct myopia.
Though the treatment itself lasts only about a minute per diopter, it takes several hours before the final change in power occurs. The power can be adjusted in 0.25-D increments. Once the patient's vision is as good as it can be, the surgeon can then irradiate the entire lens at once, effectively locking in the power adjustments.
In a small study of eight cataract patients, Arturo Chayet, MD, of Tijuana, Mexico, implanted Calhoun lenses that were deliberately off the mark, so they could later be adjusted. Postop, he used the light to adjust four patients with +1.5 D of error, two with +1 D, and two with -1.25 D. After adjusting the lenses, seven of the patients are within 0.25 D of the intended refraction, and one is within 0.5 D. Their lenses have since been locked in.
Daniel Schwartz, MD, Calhoun's founder, says his company has worked with Carl Zeiss Meditec on the development of a digital light delivery device that makes it easier to place any pattern of light on the lens, including astigmatic and multifocal patterns.
"We've now treated two patients successfully for astigmatism," says Dr. Schwartz. "We corrected one for 0.75 D and one for a diopter, and plan to treat approximately 25 additional patients in the next three months."
He says that he's not sure what the limits will be for cylindrical treatments, "but we're going to try upwards of 2.5 D, which would cover most astigmatic errors. And that's with one adjustment. We can repeat our adjustments until we're ready to lock in the power." For spherical adjustments, the limit appears to be 2 D with the initial adjustment, and surgeons can get about 80 percent of that with a second one, which translates into about 3.5 D of correction with two adjustments, either myopic or hyperopic.
Dr. Schwartz expects the lens to be released in Europe in 2005. "During 2005, we would like to do a larger series of patients, apply for CE mark in Europe, and then start U.S. FDA trials in early 2006."
• The AcrySof Toric. Los Angeles surgeon and AcrySof investigator Kevin Miller discussed data on this new lens at this past ASCRS meeting. In a multicenter study, 500 patients were randomized to receive either the AcrySof toric or a spherical lens. The treatment group received IOLs with cylindrical powers of 1.5, 2.25 or 3 D.
Three months postop, all of the toric patients and 97 percent of the sphericals saw 20/40 or better best-corrected, while 77 percent and 68 percent saw 20/20 or better, respectively. Ninety-one percent of the treatment group and 72 percent of the spherical group saw 20/40 or better uncorrected.
Twenty-nine percent of the spherical patients had greater than 1.5 D of residual cylinder, versus just 5.3 percent of the toric patients.
Alcon plans to apply for U.S. approval early this year, and hopes to launch the lens in Europe and the United States in late 2005. The approved version will most likely be a single piece, square-edged lens with a blue-blocking tint.
| National Panel Report: Which Lenses are Surgeons Using? |
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According to our latest National Panel survey, surgeons appear to be embracing the Alcon AcrySof Natural IOL in greater numbers than in last year's report, and are also receptive to the possibility of using multifocal and toric IOLs. |
