IOLs are the Future
The pipeline is flush with innovation.
BY ROCHELLE NATALONI, CONTRIBUTING EDITOR

There are close to 2,000 intraocular lenses of one sort or another in the worldwide market, according to ophthalmologist and medical device development consultant, Robert M. Kershner, M.D., and yet the literally endless pool of potentially correctable presbyopes makes research and development into new IOLs an investment worth making. Venture capitalists and ophthalmic device manufacturers are putting their money where their eyes are, and are reinvigorating a market that a decade ago threatened to languish in a sea of reimbursement woes. "The fact is," says refractive surgery veteran and fledgling IOL developer, Lee Nordan, M.D., "you cannot correct presbyopia adequately on the cornea. IOLs are the future."

This article focuses on the IOLs that are in development.

The IOL Continuum

IOLs in the pipeline represent a continuum of the groundbreaking lenses that are already out there reshaping the face of ophthalmology. Alcon's (Fort Worth, Texas) AcrySof Natural HOA aspheric optic as well as its ReSTOR lens; AMO's (Santa Ana, Calif.) Tecnis monofocal and multifocal lenses, as well as the ReZoom; Bausch & Lomb's (Rochester, N.Y.) SofPort AO and eyeonics' (Aliso Viejo, Calif.) crystalens have set new visual standards and laid the foundation for tomorrow's dual-optic, deformable and injectable polymer IOLs, as well as for the next generation of single optic phakic and aphakic lenses.

Meanwhile, these innovative IOLs are evolving in response to patient needs. For instance, eyeonics has taken its crystalens a step further with a new version called the SE System. This version extends the square-edge 360� around the entire IOL for capsular bag maintenance. Additionally, the need for cycloplegia has been eliminated. According to Richard L. Lindstrom, M.D., and other surgeons who implant the crystalens, this has significantly increased patient satisfaction immediately postoperatively. The lens has been validated for use with the STAAR (Monrovia, Calif.) Indigo Injector System, enabling the IOL to be inserted via a smaller, sub–3-mm incision. "We changed our protocol because we found that cycloplegia is not necessary. This is really a huge help to both surgeons and patients, because it simplifies the regimen, and adds a 'wow' factor from patients as they experience their new visual system," says Kathy Kelly of eyeonics, inc.

Alcon is focusing on combining the individual benefits of each of its currently available IOLs into lenses that will provide the greatest range of vision without glasses for cataract patients. For example, in March of this year, Alcon gained FDA approval of the AcrySof ReSTOR lens in a clear version, and this was followed by approval of the Natural (blue light filtering) version of the lens in August. The company is now actively working on incorporating an aspheric design into this lens, and ultimately plans to add a toric feature that will address pre-existing astigmatism.

Alcon also recently gained approval of the AcrySof Toric IOL in a clear version, and will launch it in the spring of 2006. "The main benefit of the AcrySof Toric IOL is that the acrylic material allows it to demonstrate excellent rotational stability with minimal post surgical rotation," says Richard J. Mackool, M.D. "This leads to a large and predictable reduction in the amount of residual refractive astigmatism, which significantly improves uncorrected distance visual acuity. In fact, the approved label for this states that it significantly increases spectacle independence for distance vision."

STAAR's posterior chamber Visian ICL, which is approved for use in the European Union, Korea and Canada recently received FDA notification that the lens was "approvable with conditions." The final approvable letter was expected "any day" at press time. Subject to premarket approval, the refractive phakic implant is placed in the posterior chamber to correct myopia of -3 to -15 D with astigmatism -2.5 D at the spectacle plane, and the reduction of myopia in adults with myopia ranging from -15 to -20 D with astigmatism -2.5 D at the spectacle plane. The lens can also be used to correct myopia in patients
21 to 45 years of age with anterior chamber depth of 3 mm or greater, and a stable refractive history within 0.5 D for
1 year prior to implantation.

In the meantime, STAAR recently launched its newly designed 3-piece collamer lens, the Affinity. The new design includes polyimide haptics for excellent centration and incorporates a square continuous contact edge, reducing the potential for posterior capsule opacification, as well as glare. The lens is paired with the MSI PF/TF injector and CQ cartridge, which facilitates implantation through a 2.8-mm incision.

AMO's Multifocal Tecnis lens is available just about everywhere except in the United States. "One of the problems of multifocal IOLs is their loss of image contrast. Imagine having a lens optic that has been shown to improve contrast sensitivity married to a multifocal lens to neutralize the loss of contrast. That's essentially what the Tecnis Multifocal IOL does," says Dr. Kershner. "I've reviewed optical bench studies on this lens and there is no question — the mechanical eye model doesn't lie — the image quality is excellent for both near and far," says Dr. Kershner who predicts that FDA approval of this lens isn't more than a year or two away.

In the Pipeline

David F. Chang, M.D., is working with two innovative IOLs in the pipeline that are as different as they are the same: Visiogen's (Irvine, Calif.) Synchrony and Medennium's (Irvine, Calif.) Smart IOL. While their mechanism of action is disparate, they share a goal that is common to the majority of developing IOLs: eradication of the symptoms of presbyopia.

Dr. Chang, who is the medical monitor for Visogen, says a true accommodating IOL should have several theoretical advantages over a multifocal IOL. "In addition to avoiding the halos and contrast sensitivity loss inherent in a multifocal optic, the lens does not produce a single fixed near point of focus," he says. "Instead, Synchrony may allow the patient to adjust their focus along the entire continuum of far, intermediate and near distances." The Synchrony is a single piece dual-optic IOL made of latest-generation silicone, which allows implantation through a specially designed injector system. Dr. Chang describes its design and mechanism of action as such. "The refractive shift produced by any optic movement is proportional to the dioptric power of the lens. Therefore, the anterior moving optic is a 34 D (+) lens in order to amplify the near shift produced by its forward movement, he says. "The rear optic is a minus power lens that is varied in order to achieve the net individual power required for emmetropia. The design relies upon the Helmholz theory of accommodation whereby ciliary muscle contraction reduces zonular tension, allowing the capsular bag to become lax. This allows the spring-like connecting struts to push the anterior optic forward."

Ultrasound biomicroscopy (UBM) imaging has confirmed that the front optic does move in the human eye, he says. Clinical trials are ongoing in Europe and South America, and the FDA trial is scheduled to begin within in the next 6 months.

Another dual optic accommodative IOL that reportedly holds a great deal of promise is the Sarfarazi elliptical IOL, which Bausch & Lomb has licensed. Comprised of a minus-powered optic positioned posteriorly to a positive-powered optic it is joined by compressible bridges, or haptics. This innovative lens is being implanted investigationally overseas, but is still in the feasibility stage as a project.

Dr. Chang is also on the scientific advisory board of Medennium, which is developing the Smart IOL, a unique thermoplastic accommodating lens. "This is a bag-filling IOL design that will hopefully allow the ciliary muscle to resume control of lens shape alteration," says Dr. Chang. "This, too, [like the Synchrony] would produce focus along the entire accommodative range." To meet this goal, many researchers have worked on formulating a gel that could fill the emptied bag and remain flexible." However, Dr. Chang notes, "This approach creates many new challenges: How much gel does one inject? How does one control the net resulting lens power? How does one seal the capsulotomy, and can a dense cataract be removed through a micro-capsulorrhexis that would be most compatible with injectable gel technology?" The final challenge, he says is, "How does one produce a precise optical shape with this method?"

The advantage of the Smart IOL, according to Dr. Chang, is that the hydrophobic acrylic lens can be manufactured to precise optical specifications, including power, size and anterior and posterior curvature. "However, thanks to its unique thermoplastic properties, it can then be reconfigured into a thin rod that can be implanted through a phaco incision. After implantation, warming to body temperature causes the shape to transform back to the originally designed configuration, which will completely fill the capsular bag. The material is flexible enough so that the implanted lens can change its shape. One theoretical advantage of this design is that it is compatible with current phaco methods, and a standard sized capsulorrhexis," he explains. The Smart IOL has been implanted into cadaver eye capsular bags, but must undergo further testing before human implantation can begin.

Alcon is also researching mechanically accommodative IOL designs. "The successful development of mechanically accommodative lenses will have to overcome two fundamental challenges: predictability of accommodative effect and sustainability of visual performance," says Alcon's vice president of Surgical Products Research and Development, Robert J. Stevens. "Both of these issues are the result of physiological variability across the patient pool and over time with individual patients. Our product research and development approach is designed to minimize the impact of physiological variability to improve predictability of accommodative effect and sustainability of visual performance," he explains.

Alcon also has a phakic lens in development. This lens is an anterior chamber angle-supported lens that has shown excellent visual results in early clinical studies, according to Stevens. "We are further along with the approval process for this lens in Europe than we are in the United States," says Stevens. "We think this lens will perform well and be an option for refractive surgeons when dealing with their highly myopic and hyperopic patients." This lens may be available in Europe by late 2006 or early 2007.

Thinking "Outside the Bag"

Dr. Kershner says the ideal IOL would be a single optic device that could change powers, and suggests that the ultimate "answer" lies in the form of a deformable lens. One such device, the NuLens Accommodating IOL, is in development by NuLens, Inc., (Herzliya Pituach, Israel). This IOL is reportedly the first to truly accommodate by changing its power rather than changing its position in the eye. The design concept incorporates the use of a gel-filled piston contained within the IOL, and breaks completely from conventional thought with the placement of the IOL in the ciliary sulcus rather than the capsular bag.

"It's the [gel-filled] chamber that moves in response to capsular bag movement," explains Dr. Kershner. The NuLens has been shown to work in primates and is poised to enter U.S. clinical trials within the year.

AMO is working on a deformable lens in conjunction with QuestVision (Santa Ana, Calif.). The companies entered into a 1 year research and evaluation licensing agreement and are working on a "shape-changing optic to provide accommodation, rather than an axial movement used in single- or dual-optic alternatives," AMO President and CEO Jim Mazzo, said in a press release.

Another deformable IOL with excellent potential, according to Dr. Kershner, is PowerVision's (Belmont, Calif.) FluidVision IOL. "This lens has an optic that has a deformable surface, but the deformation of the surface is very closely controlled by a hydraulic. There are reservoirs in the IOL's haptics, and in response to contractions in the ciliary body, these reservoirs dump their fluid into the center of the lens, which then deforms the anterior surface by a predictable and controlled amount to add additional power for near vision," Dr. Kershner explains.

Louis D. "Skip" Nichamin, M.D., reported on this lens at the annual meeting of the American Society of Cataract and Refractive Surgery. Dr. Nichamin presented data from modeling studies that demonstrate by harnessing natural forces in the eye, the FluidVision should be able to create an accommodative range of up to 10 D. It is possible that the first human eye procedures will be performed in late 2006.

Refractive surgery veteran Lee Nordan, M.D., is championing the Vision Membrane lens, an anterior chamber phakic IOL in development by Vision Membrane Technologies Inc. (Carlsbad, Calif.), of which he is president and CEO. "What's unique about this lens," says Dr. Nordan, "is that it is the same thinness for all powers. The beauty of this is that the way it sits in the anterior chamber is basically a constant, and regardless of the power, there's the same amount of clearance from the endothelium," he explains.

The lens' patented multi-ordered diffractive optics (MOD), provide the benefits of diffraction — near and far vision — without the drawbacks of chromatic aberrations. "We think we have something here. This is really next generation technology in that we can correct presbyopia but do it in conjunction with correcting distance vision as well. I'm not saying we're going to wipe out presbyopia, but we can eliminate the symptoms," he says.

Dr. Nordan expects to start a CE trial within the next 3 to 6 months. "We're in a proof of concept phase. We've implanted seven of the lenses [overseas] and 1 year postoperatively they look excellent," he says.

A general consensus exists that the rewards of microincision IOL implantation are worth reaping. Innovative developing IOLs that lend themselves to that goal include the Lenstec's (St. Petersburg, Fla.) Tetraflex and ThinOptX. The Tetraflex is an acrylic, square-edged, 1-piece microincision- accommodating lens with equiconvex optics. Unique haptics and a 5° anterior angulation reportedly enable the lens to move forward during the accommodating process. This IOL is in clinical trials in Europe.

The ThinOptX IOL takes the microincisional label to a whole other level, says Dr. Kershner, because it is infinitesimally thin. "The thin optic is created through the use of the Fresnel Prism optical design, and in so doing creates an optic that has no central thickness to it. It's very thin and flexible like a sheet of cellophane, so it can be rolled up very tight and injected in the eye through less than a 1-mm incision," says Dr. Kershner.

Another truly innovative and potentially groundbreaking IOL is Calhoun Vision's (Pasadena, Calif.) Light Adjustable Lens, a 3-piece IOL, made of a photosensitive silicone material. The unique property of this lens is that once implanted its power can be titrated through the use of UV beams from a light delivery device.

The "Holy Grail," says Dr. Kershner is an IOL that will change focus, have the optical quality of a standard monofocal lens and provide near and distance vision all in one package. Once that ideal is achieved, he adds, the challenge will be to get it to work inside the eye. OM