Phakic IOLs: Countdown to Approval
Will they fill a narrow niche or rival LASIK?
By Jerry Helzner, Associate Editor

Sometime late next year or in early 2004, an ophthalmology milestone will be reached in the United States. The first phakic IOL is expected to win FDA approval for general use in this country. The great majority of the initial implantations will be in high myopes between the ages of 21 and 45 with up to 2D of astigmatism, and with refractive errors of from approximately -8D to -20D. Also currently under development are toric versions of phakic IOLs, phakic lenses that will correct hyperopia, and multifocal phakic IOLs for correcting presbyopia.

As you know, phakic IOLs are implants capable of correcting refractive error without removal of the natural crystalline lens and without affecting the accommodative powers of the eye. Though phakic IOLs are designed to remain in the eye for decades, they can be removed fairly easily if complications arise or if a patient experiences a significant vision change. In this article, I'll describe the current state of phakic IOL technology, improvements that can be expected in the near future, and the outlook for phakic lens acceptance in the refractive marketplace.

STAAR Surgical's ICL

Who's in the race

The phakic lenses that are likely to be approved first already have a track record. They've been in wide use internationally and will have 3 years of U.S. clinical data on record by the time they're submitted for FDA approval in the next several months. It's generally expected that the first phakic IOL to be approved in this country will be STAAR Surgical's ICL, a foldable, posterior chamber lens made of a collamer material, which is currently completing its U.S. clinical trial. Close behind in completing its trial is the Artisan, a nonfoldable, iris-fixated PMMA lens, backed by Ophtec USA and Advanced Medical Optics (AMO), a newly created company which was formerly part of Allergan. The Artisan will be marketed in this country by AMO under the name Verisyse. The only other lens currently in a Phase III clinical trial in the United States is CIBA Vision's PRL manufactured by Medennium, a foldable, posterior chamber, customized silicone lens with a high refractive index. The PRL is about 2 years behind the ICL and 18 months behind the Artisan in terms of meeting FDA requirements for clinical data and follow-up.

Other companies also in the race include:

• Ophthalmic Innovations International (OII), which has launched its angle-fixated Phakic 6H2 heparin-treated phakic IOL in Europe and is in Phase II trials in this country
• Tekia, Inc., backer of the angle-fixated Kelman Duet two-piece phakic IOL that's assembled in the eye
• Alcon, Inc., which confirmed that it's developing several phakic IOL designs, including at least one anterior chamber lens. The company says its goal is to improve on current phakic IOL technology
• ThinOptX, which says it's in the early stages of developing what it calls a "totally different" design using its proprietary thin lens technology.

In addition, CIBA Vision owns the internationally marketed Vivarte angle-fixated, foldable phakic IOL. The company also has a presbyopic phakic IOL that will launch in Europe this fall.

An evolving technology

In interviews with more than 20 refractive surgeons and phakic IOL developers focusing on the potential for phakic IOLs in the United States, Ophthalmology Management found widespread agreement on some questions relating to this technology and a wide divergence of opinion on others. For example, all concurred that phakic IOLs offer excellent vision quality and might be an appealing vehicle for cataract surgeons to develop a refractive practice. On the other hand, we encountered hot debate over the preferred positioning in the eye for phakic IOLs.

Following are the areas of agreement:

	Ophtec's Artisan

Phakic IOLs are coming along at the right time. George O. Waring III, M.D., professor of ophthalmology and director of refractive surgery at the Emory University School of Medicine in Atlanta, says refractive surgery in the United States is evolving in three stages.

"First came acceptance," says Dr. Waring. "In the 1990s, refractive surgery was accepted by the public and the ophthalmic community. In the next stage, LASIK became the standard. And in the third stage, phakic IOLs will take a large part of the LASIK market over the next 5 years. Surgeons participating in the clinical trials are using phakics for -8D now, but that could go lower."

Jacob Feldman, CEO and president of phakic IOL developer Medennium Inc., agrees. "Phakic IOL acceptance will grow as surgeons and patients gain confidence in the technology," says Feldman. "With phakic IOLs, we will be able to treat patients with any diopter of refractive error. And surgeons are already very comfortable implanting IOLs. It's something they're used to doing. Some doctors will be much more comfortable using phakic IOLs than doing LASIK."

Phakic IOLs meet a need. Just about everyone interviewed agrees that phakic IOLs will fill an important niche in the refractive marketplace, initially being best suited for high myopes from ages 21 to 45 and moderate myopes who aren't good candidates for LASIK. In the three major U.S. clinical trials for phakic IOLs, patient satisfaction is reported as very high and overall vision quality exceptionally good. More than 90% of these formerly high myopes have achieved uncorrected vision of 20/40 or better.

"Phakic IOLs will be a great tool for enabling us to correct extreme myopia," says Richard L. Lindstrom, M.D., clinical professor of ophthalmology at the University of Minnesota and managing partner, Minnesota Eye Consultants. "However, I do see this as a niche technology. Phakic IOLs have been available in Europe for years and have only captured about 5% of the total refractive market there." (For further discussion of this issue, see "How Important Is Being First".)

Dr. Lindstrom has participated in the Artisan trials and has praise for the one-size-fits-all, anterior-positioned lens, which clips directly onto the periphery of the iris.

"I'm impressed and pleasantly surprised with the Artisan. It's been performing very well," he notes. "The Artisan requires a technically demanding implantation, but it doesn't have any major warts. I think it will be competitive in this arena."

Dr. Waring, though more enthusiastic about the potential for phakic IOLs, says the technology must continue to improve if his high expectations are to be met.

"This first generation of phakic IOLs won't give surgeons everything we want. We will want to have access to toric versions, and Artisan will need to get its foldable version approved because surgeons find smaller incisions preferable."

Dr. Waring asserts that phakic IOLs can provide better vision than LASIK without patients having to worry about possible flap complications.

And I. Howard Fine, M.D., clinical associate professor of ophthalmology at the Casey Eye Institute, Oregon Health and Sciences University, also sees a bright future for phakic IOLs.

"LASIK has an element of unpredictability," says Dr. Fine. "It makes more sense to correct refractive error by addressing the lens."

Dr. Fine has implanted a number of STAAR ICLs and reports excellent results.

The CIBA Vision PRL manufactured by Medennium

Cataract surgeons will be able to make an easy transition to phakic IOLs. Darcy Smith, vice president of refractive business for STAAR Surgical, says most experienced cataract surgeons should be comfortable with implanting the posterior-positioned STAAR ICL.

"There is a learning curve for implanting our ICL and surgeons will have to take a training course and be certified," she notes. "But the ICL is foldable and injectable. They won't find it too different from what they've been doing."

"Artisan implantation has a steep, but short learning curve," says Rick McCarley, president of Ophtec USA. "Most surgeons have never used an Artisan design that's iris-fixated in the anterior chamber, but after training we find they have no difficulty in implanting the lens."

Phakic IOL manufacturers are counting on cataract surgeons becoming major advocates for their lenses. It's estimated that almost 12,000 ophthalmologists in the United States either don't perform laser vision correction or haven't made a major financial commitment to the equipment required to perform LASIK. If they see that they can very easily incorporate phakic IOLs into their practices, the number of phakic implants could soon easily exceed initial estimates of 50,000 to 100,000 patients per year.

"The cataract surgeons are the real 'wild cards' in estimating phakic IOL acceptance," says Dr. Lindstrom. "It's going to be difficult to estimate procedure volume until we see how strongly they embrace phakic IOLs."

A debate rages

But while no one doubts that phakic IOLs will have their place in the big picture of refractive correction, it's difficult to get any agreement on which phakic IOL technologies will prevail in the longer run. The biggest area of controversy, by far, is over the positioning of the phakic IOL in the eye. (Another area of contention, concern over potential endothelial cell loss in anterior chamber implants, has been put to rest by the industry but is still under study by the FDA.)

	Tekia's two-piece Kelman Duet

"It's now the great AC (anterior chamber) vs. PC (posterior chamber) debate," says Don Ferguson, vice president of global marketing for OII, which developed the Phakic 6H2, an angle-fixated anterior chamber phakic lens.

"Posterior chamber phakic IOLs have a history of causing cataracts in some patients," says Ferguson. "That will always be a concern to surgeons. The anterior chamber is a safer working area, giving surgeons a greater margin for error."

But John A. Vukich, M.D., surgical director of the Davis, Duehr, Dean Center for Refractive Surgery in Madison, Wis., and medical monitor for the North American clinical trials for STAAR Surgical's ICL, says the company's Version 4 ICL, a posterior chamber lens, is showing a far lower incidence of opacities in clinical trials than previous versions of the ICL.

"The vault was lengthened in the new design, and it's made an enormous difference," says Dr. Vukich. "We're seeing lens opacity in less than 1% of the patients in the trial."

And Jacob Feldman of Medennium says the PRL, also a posterior chamber lens, is light and essentially friction-free, with a design that keeps it from rubbing against eye structures.

"We have the only phakic lens that's not permanently fixated," says Feldman. "It's not attached to anything. It moves with the dynamics of the eye. We believe our design reduces the possibility of complications."

Every surgeon we interviewed acknowledged the cataract concern associated with posterior chamber phakic lenses.

David R. Hardten, M.D., clinical associate professor of ophthalmology at the University of Minnesota and director of refractive surgery, Minnesota Eye Consultants, reflected a typical surgeon's view of safety issues associated with posterior chamber phakic IOLs.

"They're going to have to show us that they can reduce the incidence of lens opacities to a number that most surgeons and patients would find acceptable," says Dr. Hardten. "I would think about 1 to 2% would be considered reasonable."

Dr. Lindstrom adds another cautionary note.

"Complication rates are often lower in studies than they are in general usage," he observes. "In the studies, you tend to have the most highly skilled, highly motivated surgeons. The jury is still out on posterior chamber phakic lenses until we have more follow-up data."

Other designs also draw fire

Meanwhile, anterior chamber lenses such as OII's Phakic 6H2, the Kelman Duet and the Vivarte, with so-called angle-fixated designs, also carry some negative baggage.

"An angle-fixated lens is the easiest for a surgeon to implant, but they have a history of causing pupil ovalization," says Dr. Waring.

"The angle-fixated lenses have gotten better, but pupil ovalization is still a problem," echoes Dr. Lindstrom.

Dr. Fine says angle-fixated phakic lenses "have a variable history of both pupil ovalling and glare."

Gene Currie, president of Tekia, Inc., which is developing the Kelman Duet, says his angle-fixated lens won't cause pupil ovalization if the eye is measured accurately and a proper-sized haptic is implanted.

"Because the haptic and optic are separate pieces in our design, we will offer a number of different-sized haptics to surgeons," says Currie. "This will allow them to achieve the right fit. Actually, the biggest hurdle for us is educating surgeons to the fact that the Kelman Duet -- which has been compared to a ship-in-a-bottle -- can be easily assembled in the eye."

Jorge L. Alio, M.D., Ph.D., professor and chairman of ophthalmology, Miguel Hernandez University, Alicante, Spain, has implanted the Kelman Duet in about 10 patients. He says surgeons who have attended wet labs are surprised at the ease with which a Kelman Duet can be implanted. He says the Duet's modified haptic and use of flexible materials should minimize the chance of pupil ovalization.

"If the first haptic isn't exactly the right size, you can easily go in and change it," says Dr. Alio. "You can also change the optic if the patient's vision changes. But I would only change the haptic once and the optic once in a patient's lifetime." Dr. Alio says the Kelman Duet could prove especially useful for children and pre-presbyopic individuals.

David J. Schanzlin, M.D., professor of ophthalmology at the University of California, San Diego, and lead investigator for OII's Phakic 6H2 trial, says the 6H2 addresses the issues of pupil ovalization and glare that have plagued angle-fixated phakic IOLs in the past.

"The lens has a soft acrylic polymer haptic to deal with the ovalization problem," says Dr. Schanzlin. "It also has a thinner optic to reduce glare. And a foldable version of the 6H2 is being developed."

The Vivarte from CIBA Vision is a foldable, anterior chamber phakic IOL. "I agree that sizing and foldability are key," says Pat King, head of global marketing, CIBA Vision Surgical. "Our experiences with the Vivarte in Europe have shown very minimal occurrences of pupil ovalization."

The iris-fixated Artisan comes in for some criticism, as well. Dr. Fine thinks the large incision required by the current, nonfoldable version of the Artisan is a major drawback.

"The Artisan could be one of the winners, but they'll need to get a foldable version out there to be competitive," he says.

And, as stated previously, the Artisan is considered the most technically challenging of the phakic IOLs to implant.

	OII's Phakic 6H2

"I'm very much aware of the positives and negatives that have been associated with every type of phakic IOL design," says Rick McCarley of Ophtec USA, who's shepherding the Artisan lens through its U.S. clinical trials. "Some of our detractors have claimed that the Artisan lens is an iris-clip lens, similar to lenses that caused problems in the 1970s. Actually, it's attached to the periphery of the iris and it doesn't move. We also recognize that the trend is toward small-incision surgery, and that's why we'll soon have a foldable version. But surgeons can use the larger incision to correct astigmatism if they make the incision at the site of the astigmatism, on the steep meridian. So what some may see as a drawback can actually be an advantage."

Despite the disagreements over whose lens is best, McCarley thinks the future success of phakic lenses is assured.

"Phakic IOLs will be able to take on LASIK in a head-to-head competition, and even with the addition of custom ablation, phakic IOLs will be able to deliver more benefits to patients, and to surgeons," he asserts.

Combining technologies

In the end, the phakic IOL and the laser may turn out to be complementary technologies rather than rivals.

Surgeons who have participated in the U.S. clinical trials for phakic IOLs say that about 25 to 30% of the patients who receive the phakic lenses still have a small degree of refractive error and many have residual astigmatism. Though it's not permitted during the trials, surgeons see a LASIK or PRK "tweak" as the way to give those patients even better vision."

"I think we'll be using a phakic IOL and laser touch-up to provide many of our patients with the greatest overall vision benefit," says Dr. Schanzlin. "Eventually, it's all going to be combined."