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Presbyopia - Corneal inlays: the next big thing?

Posted by Michelle Dalton EyeWorld Contributing Editor

Experts cite the reversibility, easy centration, and promising study results that may make corneal inlays as big as LASIK

An artist’s rendering of the scleral expansion band
Source: Refocus Group

The AcuFocus corneal inlay, after successful implantation
Source: Richard L. Lindstrom, M.D.

Pre-op and post-op (1 month) wavefront topographies after the Biovision corneal inlay was inserted
Source: Michael Gordon, M.D.

AcuFocus corneal inlay
Source: Richard L. Lindstrom, M.D.

The Revision hydrogel 2 mm corneal inlay for the treatment of presbyopia
Source: Stephen G. Slade, M.D.

The Revision hydrogel corneal inlay, after staining for easier visualization Source: Stephen G. Slade, M.D.

An illustration showing how the AcuFocus ACI 7000 corneal inlay works
Source: Daniel S. Durrie, M.D.

In the near future, surgeons will be able to add corneal inlays and scleral spacing procedures to laser options already offered as treatments for presbyopia.

According to Richard L. Lindstrom, M.D., founder of Minnesota Eye Centers, Minneapolis, and president of ASCRS, there are 44 million naturally occurring emmetropic presbyopes in the U.S., about 6 million emmetropic presbyopic post-LASIK individuals, and 12 million emmetropic presbyopic post-cataract surgery patients.

“We have a lot of tools at our disposal to treat presbyopia, but we really haven’t educated patients about presbyopia, and physicians don’t yet fully understand it’s a progressive disease,” said Daniel S. Durrie, M.D., clinical professor of ophthalmology, University of Kansas Medical Center, and president, Durrie Vision, Overland Park, Kansas.

The classic cataract/refractive surgeon has been trained to “see the patient and get them out of the office. The presbyopic patient stays in your office like a glaucoma or retinal patient,” Dr. Durrie said.

Currently, three different corneal inlays are being developed: the AcuFocus/Bausch & Lomb ACI 7000, the Invue intracorneal microlens (Biovision, Brugges, Switzerland) and the PresbyLens (ReVision Optics, Lake Forest, Calif.).

Small diameter corneal inlays “are all going to be somewhat similar,” said Elizabeth A. Davis, M.D., a partner at Minnesota Eye Consultants. Those under current investigation are all designed to be implanted in the non-dominant eye. “Any time something is done to just one eye, there’s not as much benefit,” she said. “And they all have some compromise with quality of vision.”

“I am excited about corneal inlays. For one, they can be placed at the same time as LASIK,” said James J. Salz, M.D., Laser Vision Medical Associates, Beverly Hills, Calif. “You can correct –5 D with the laser and put an implant in and offer a potentially bright future to the patient.”

The primary remaining problem is biocompatibility, said Stephen G. Slade, M.D., director of Laser Center of Houston. “Once we find something in a material the eye will tolerate, inlays will become the most amazing platform for the correction of presbyopia,” he said.

“They’ve got all the advantages and fewer disadvantages of other technologies. With keratophakia, if you can make a flap, lay a lens on the stromal bed—perfectly centered—and lay the flap back, that can be removed if necessary—that’s perfection. Keratophakia has all three. Right now, though, nothing has realized the promise of keratophakia.”

Corneal inlays

The ACI 7000 is a small diameter aperture optic, said Dr. Lindstrom, and the furthest along in clinical trials. “It increases the depth of focus by using a pinhole optic,” he said. The inlay has a 1.6 mm center with a 3.6 mm surround. Peripheral rays are obscured and the central rays pass unaffected.
“It generates improved near vision of about 1.5 D add, and does it with no measurable loss of distance vision,” Dr. Lindstrom said. Placed on the non-dominant eye, a corneal flap is cut as in standard LASIK, the inlay is placed on the stromal bed, and the flap is then replaced. “Patients have continuous improvement for up to a year,” he said. “Placement of the inlay is important. Most patients have a little loss of quality of night vision, but it’s not a big obstruction. Most people would not want this in both eyes.”

The ACI 7000 “doesn’t change corneal power but depth of focus, and patients are getting pretty darned good vision at distance on the eye chart,” Dr. Durrie, the medical monitor for the inlay, said. In trials, patients had good range of vision and “their defocus curve is very broad,” he said.
“It’s a pinhole effect, and how far can you take that pinhole?” Dr. Slade said. “If it doesn’t work, or if it only works for 30%, what kinds of improvements can there be? Like we had with RK, how far can we push that technology? If the company finds they need to make it better, where is the

room or pathway to improve the pinhole?”

Not a complete naysayer, Dr. Slade said he likes that the inlay can be perfectly centered and removed if necessary. “I truly like keratophakia,” he said. “I’m enthusiastic about the AcuFocus, but I still have questions,” he said.

Marguerite McDonald, M.D., clinical professor of ophthalmology, Tulane University, New Orleans, and Ophthalmic Consultants of Long Island, Lynbrook, N.Y., said the Food and Drug Administration has been “quite surprised at the early data out of the U.S. [AcuFocus] trials.” The newest iteration is only 5 microns thick. “The only downside is there is a little light coming into the eye, it’s a little darker,” she said. Among the upsides she cited, however, is that it’s not diffraction limited.

“It has a controlled aperture, with a big central 1.5 mm. There are numerous little holes that will enhance the nutritional flow from the anterior chamber,” she said.
The other two inlays are both hydrogel-based, Dr. Lindstrom said. With the Biovision InView inlay, the surgeon positions the lens in a tunnel about 200-400 microns deep, he said, in the center of the cornea. Like the AcuFocus, stable centration is easy, and if necessary, the lens can be removed as well.

“This lens is great for the emmetropic presbyope whose cornea is the proper power for distance and who doesn’t have astigmatism,” Dr. Lindstrom said. “It’s the same concept as the multifocal IOLs, but it’s creating a multifocal cornea. It’s giving really good near acuity with a small loss of distance, about 1-2 lines, in current trials.” Because the inlay is creating a multifocal cornea, however, it does have all the potential side effects of multifocal optics, just as the IOLs do, he said.

Although not yet in U.S. clinical trials, the InView is a 3 mm diameter, and “the center 1.8 mm has no power. There’s a ring of add around that, anywhere from 1.2 D to 5 D,” said Michael Gordon, M.D., a founder of Gordon-Binder-Weiss Vision Institute, San Diego. “The international trial results have been excellent. There’s quick recovery; patients don’t have to wait to get the results; the average is about 2-4 weeks. There’s been little night glare reported, too.”

He said the inlay is implanted in a tunnel “at 250 microns mid-stroma. There’s a special instrument that creates the 3.5 mm tunnel to implant the 3 mm lens. It’s a very simple technique.” Dr. Gordon added the implants are 20 microns thick, making them very well tolerated.

The ReVision Optics (Lake Forest, Calif.) inlay is used to change the anterior curvature of the cornea when placed under a LASIK flap, Dr. Lindstrom said. At 1.5 mm diameter, it’s designed to provide a central near add zone and a paracentral intermediate zone, allowing the remaining cornea to be used for distance vision.

“The current 1.5 mm lens gives the cornea a hyperprolate shape,” Dr. Gordon said. “The beauty of any of these procedures is that they’re reversible and exchangeable.”

Dr. Slade, an investigator for ReVision, said the inlay has gone through several iterations, but the latest is about 2 mm. “It’s a hydrogel-like material that’s laid on the bed, centered under the laser. So far, our main metric is how many lines of near do you gain compared with how many lines of distance do you lose, both monocularly and binoculary? With monovision, it’s about 1:1. What you really want is something that expands the field of vision, and we think this current design can do that.”

Implantation is simple and similar to the others for the non-dominant eye, Dr. Slade said. “You make a flap, lay the lens on the bed, center it, and replace the flap.” Currently, the inlay calls for a 5-6 mm flap, “then we make a little pathway through and into the cornea like a channel, with the incision out by the limbus,” he said, noting it’s somewhat like making a 1 mm channel that looks like a lollipop which then expands to 3 mm, centered over the pupil.

What excited Dr. Slade about the inlay is “if we find aberrations are a problem, we’ll be able to fix that. We can induce coma if we want.”

Scleral spacing procedures

Scleral spacing procedures are also in trials here in the U.S.; the PresView (Refocus Group, Dallas) consists of four separate plastic PMMA segments that are implanted in the scleral surface, causing a slight lift in the sclera.

Barrie D. Soloway, M.D., director of vision correction at The New York Eye and Ear Infirmary, and assistant professor of ophthalmology at The New York Medical College, New York, and an investigator for Refocus, said trial results have shown “around 80% are 20/40 or better, but one in every seven is not getting enough of an improvement.”

He said the protocols are somewhat limiting, in that only emmetropes are allowed, but that so far, “when patients are doing well, they’ve got a good range of vision throughout. These are removable, and we’re not touching the visual axis. To date, no patients in the U.S.A. FDA [Food and Drug Administration]-monitored IDE [Investigational Device Exemptions] or international clinical trials have any loss of distance VA, nor have we seen any contrast sensitivity losses.”

He prefers the PresView to inlays, as “I haven’t been convinced the inlays are the be-all and end-all. Inlays have a role if the patient is also undergoing LASIK.”
In the U.S., Phase I and II trials were one-eyed implantation in the dominant eye only; Phase III will allow implantation in both eyes, Dr. Soloway said. Others are not as convinced that scleral spacing procedures are viable, although Dr. Durrie puts the overall category in his “interesting to watch” group.

“Everyone who studies the field of scleral weakening and expansion has seen a positive outcome in some patients, but the percentage of success rates has put it on the back burner as a forefront option,” Dr. Lindstrom said. “Several companies are working on laser weakening of the sclera. Right now, it’s not totally dead, but its future is moribund. To succeed, it needs to be less invasive with more consistent outcomes.”
Dr. Salz believes the procedure yields more of a placebo effect than a measured one.

“When accommodation is studied, the procedure doesn’t really work,” he said. “I don’t like the idea of putting plastic in the sclera just to get rid of glasses.”
In short, Dr. Gordon said, “there has not been anything to my knowledge that’s been acceptable and stood the test of time with scleral spacing.”

As for which technology may be best accepted, “whichever one works the best,” Dr. Salz said. “Patient selection is going to play a role.”

Future technologies

In the “far future,” Dr. Lindstrom said, femtosecond lasers may be able to treat presbyopia through what he calls “radial lensotomy—the incisions are placed in a radial fashion in the natural lens. In the lab, it appears to increase elasticity in the lens.”

Other techniques on the horizon include laser energy to break the bonds and put antioxidants into the lens to restore elasticity, he said. “In the lab, we’ve shown it can be done,” Dr. Lindstrom said.
Finally, he’s encouraged by vision training results with NeuroVision (Singapore). “It’s good for about 2 lines, maybe 0.5 D,” he said. “I think it will be most useful as an adjunct to other therapies.”

Ideally, said Dr. Davis, bilateral procedures are needed to correct presbyopia. “I believe we’re moving in that direction, and that it will be a lens-based procedure. Accommodation is a dynamic process and what you can carve on a cornea or implant is static. Somehow removing the rigid lens of eye and replacing it with something that’s pliable would be best.

You’ll need that full range of focal points to return,” she said. Each of the current technologies will have a small piece of the presbyopic market, Dr. Davis said, “but none is a home run. Each will work for some patients and they’ll be happy. The ultimate treatment has yet to be put forth.”