Read Refractive Surgery Outlook

Corneal Inlays Have Reached a Tipping Point

By Linda Roach

Seven years after the first corneal inlays won the European CE Mark, this presbyopia treatment appears to be coming of age.

Most international refractive surgeons took a wait-and-see approach when the first inlay approval came in 2005. That was for the Acufocus ACI7000 (AcuFocus, Irvine, Calif.) small-aperture corneal inlay, which since has been renamed the KAMRA.

This cautious reaction was repeated when three other inlays also won the CE mark:

• Vue+ Corneal Inlay, a 2-mm hydrogel disc that alters the central corneal curvature to improve near vision (formerly PresbyLens; ReVision Optics, Lake Forest, Calif.).
• Flexivue Microlens, a bifocal inlay made of hydrophilic polymer (Presbia, Los Angeles, Calif.).
• Icolens, another bifocal inlay, made of hydrophilic acrylic (formerly InVue; Neoptics AG, Hunenberg, Switzerland).

Early Failure

Although corneal inlays were first described in 1949, early models failed due to refractive unpredictability, progressive loss of visual acuity, decentration, haze and perilenticular opacity.¹

However, attitudes in the refractive surgery community began to thaw a couple of years ago, as more positive peer-reviewed studies, most of them concerning the KAMRA, were published.

Small-Aperture Optics

Analysis of the 507-subject multinational, Phase III FDA trial of the AcuFocus inlay is now underway, and the company will submit a request for U.S. marketing approval soon, according to an AcuFocus spokesman. While KAMRA is the most commonly used corneal inlay internationally, it would be the first such device approved in the US.

Instead of multifocality, the KAMRA harnesses the principle of small-aperture optics to increase the eye’s depth of focus and thus improve near and intermediate visual acuity, similar to the f-stop of a camera. It is a dark, flat, annular device, 5 microns thick, and meant for placement in the nondominant eye. It has an outer diameter of 3.8 mm and a 1.6-mm aperture at the center.

Internationally, the accumulation of positive clinical results about the KAMRA^1-9 appears to be moving the general acceptance of corneal inlays towards a “tipping point,” said George O. Waring IV, MD, assistant professor of ophthalmology and director of refractive surgery at the Medical University of South Carolina Storm Eye Institute, and medical director of the Magill Vision Center, both in Charleston.

Though the other inlays have their supporters, enthusiasm appears to be running highest for the KAMRA. “There’s an exponential increase going on. The volume is growing fast, particularly in Japan,” said Dr. Waring, who is the worldwide surgical monitor for company-sponsored clinical trials of the inlay.

10,000 Eyes and Counting

Outside of clinical trials, refractive surgeons around the world have implanted more than 10,000 KAMRA devices, according to AcuFocus. Dr. Waring adds another anecdotal milestone: “Now there are a number of refractive surgeons who actually have the device implanted in their own eye.”

The current, third generation of the KAMRA (ACI7000PDT) is still made of polyvinylidene fluoride (PVDF), into which nanoparticles of carbon are incorporated to make the material nearly opaque. To facilitate nutrient flow, the ring is microperforated with five times as many randomly-distributed holes as the earlier model; 8,400 total, each 5 to 11 microns in diameter.

The newest version is thinner than earlier iterations, at 5 microns, and is implanted deeper in the cornea, at about 200 microns, to preserve distance acuity by minimizing its impact on corneal topography. Implanted at this depth, it also allows for better flow of nutritious aqueous humor to the epithelium. Outside of the trials, some surgeons are placing the KAMRA even deeper. In Salzburg, Austria, refractive surgeon Alois K. Dexl, MD, MSc, said he prefers a depth of 270 microns.

Dr. Dexl is part of the Paracelsus Medical University group, led by Gunther Grabner, MD, that has implanted KAMRA inlays in 100 clinical trial subjects and in another 20 to 40 patients outside of trials.

Flexivue’s Bifocal Approach

The Flexivue Microlens is a hydrophilic bifocal lens with a plano central zone and a refractive peripheral zone. It is 3 mm in diameter, with an edge thickness of 15 microns and is placed into an intracorneal pocket created by a femtosecond laser at a depth of 280 microns.

Published literature is sparse.¹⁰ The company says Flexivue has been implanted in more than 500 eyes in 12 countries, with some lenses in place for more than five years.

InVue/Icolens Offers Another Bifocal

The Icolens (formerly called InVue) is a transparent, hydrogel-based disc with a 3-mm diameter and thickness of 15 to 20 microns, depending on the add power. Formerly owned by BioVision AG, the inlay was acquired by Neoptics AG and renamed. The company reports that clinical trials are ongoing, but little peer-reviewed literature has been published.¹¹

The central 1.8-mm diameter area of the inlay is plano, surrounded by an annular peripheral zone with add power of +1.25 to +3.00 D in 0.25-D increments. At the center is a 0.15-mm pinhole, which enables passage of oxygen and nutrients into the cornea.

Vue+ Elevates the Central Cornea

Placed underneath a regular LASIK flap, the 2-mm hydrogel Vue+ (formerly PresbyLens) alters the cornea’s central curvature, adding near and intermediate focusing power at the center. Follow-up and analysis of data from the Phase II FDA trial in the U.S. are not complete, and peer-reviewed literature on this inlay is limited.

Y. Ralph Chu, MD, a cataract and refractive surgeon in Bloomington, Minn., implanted 13 Vue+ devices more than a year ago as part of the FDA trial.

Anecdotally, he said the inlays made a positive impression. “The inlay changes the central power of the cornea but does not induce monovision. My patients’ refractions stayed very balanced, and satisfaction appeared to be really high,” he said.

What the Data Say

The following table summarizes the most recent available figures published by peer-reviewed journals detailing the visual outcomes after inlay surgery:

Mean Visual Outcomes in Emmetropes

Clinical Potential

“They’re all important technologies,” Dr. Waring said of the available inlays. “AcuFocus has the benefit of being the furthest down the U.S. regulatory pipeline, and it has most of the published data, so we have a really good understanding of safety and efficacy. But I believe that they all have potential.”

Dr. Chu agreed about the inlays’ potential. “I think the take-home message for refractive surgeons is that this new generation of corneal inlay technology is promising, and they should keep an eye on it,” he said.

Presbyopia Surgery Evolves

“It is important to realize that great advances in the surgical correction of presbyopia have occurred over recent years. Because the disorder is ubiquitous, it is becoming a significant part of the subspecialty of lens and corneal refractive surgery,” Dr. Waring said.

“But the overall benefit of corneal inlays, relative to other technologies, makes them one of the most effective presbyopia treatments available, particularly during the precataract decades,” he said.

Reversability

One of the most valuable characteristics of treating presbyopia in this manner is its reversibility, Dr. Dexl said.

“A refractive procedure that does not make an irreversible change to the cornea will always be preferable,” he said. “Compare the corneal inlay to other procedures, such as a multifocal intraocular lens or presbyLASIK — those are not so easy to reverse. It is very easy to remove an inlay from the cornea.”

The Future of Corneal Inlays

Beyond Emmetropia. Prospective trials of inlays so far have enrolled only emmetropes. But what about the refractive needs of myopes and hyperopes with presbyopia?

Physicians at the high-volume Shinagawa LASIK Center in Tokyo are attempting to answer this question. In a paper published this month in the Journal of Cataract & Refractive Surgery, the authors report good visual results in presbyopic patients who had corneal inlay placement performed simultaneously with bilateral LASIK to correct myopia and hyperopia.¹²

Six months after surgery, 64 of the original 180-person cohort returned for follow-up. They experienced a mean improvement in logMAR near UCVA of 7 lines in hyperopic eyes, 6 lines in emmetropic eyes and 2 lines in myopic eyes. The mean logMAR distance UCVA improved by 3 lines, 1 line and 10 lines respectively.

Monocular vs. Binocular. Some researchers suspect that if a single implant lessens presbyopia, perhaps the patient would see even better with two of them. No company-sponsored clinical trials have been reported so far.

However, Dr. Chu said he has heard that a few international ophthalmologists have begun testing this approach using the Vue+ inlay. He identified one of them as Enrique Barragan, MD, medical director of Laser Ocular Hidalgo, in Monterrey, Mexico. Dr. Barragan, who is a member of the ReVision’s Medical Advisory Board, has not published any results.

Doctor, Heal Thyself. Perhaps the future of corneal inlays will bring more cases like that of Dean Corbett, BSc, MBChB, FRANZCO, a refractive, cataract and glaucoma surgeon in Auckland, New Zealand.

An investigator in the AcuFocus clinical trials, Dr. Corbett traveled to the Shinegawa clinic in Japan to have an inlay implanted in one eye. “For me, the inlay has allowed good visual function for all my daily work activities. It has enhanced both my near and distance vision, and has been very well tolerated,” he said.

Option to Upgrade. Dr. Corbett said he valued the procedure’s reversibility not for fear of a bad outcome, but because, many years from now, he wants to be able to replace it with something better.

“An inlay to treat presbyopia has to be removable, so as to allow patients the opportunity in the future to have access to exciting new IOL technologies,” Dr. Corbett said. “A corneal inlay is a reversible—or better described, an upgradable—treatment for presbyopic symptoms.”

References

1. Waring GO, 4th. Correction of presbyopia with a small aperture corneal inlay. J Refract Surg. 2011;27(11):842-845.

2. Yilmaz OF, Bayraktar S, Agca A, Yilmaz B, McDonald MB, van de Pol C. Intracorneal inlay for the surgical correction of presbyopia. J Cataract Refract Surg. 2008;34(11):1921-1927.

3. Seyeddain O, Riha W, Hohensinn M, Nix G, Dexl AK, Grabner G. Refractive surgical correction of presbyopia with the AcuFocus small aperture corneal inlay: two-year follow-up. J Refract Surg. 2010;26(10):707-715.

4. Dexl AK, Seyeddain O, Riha W, Hohensinn M, Hitzl W, Grabner, G. Reading performance after implantation of a small-aperture corneal inlay for the surgical correction of presbyopia: Two-year follow-up. J Cataract Refract Surg. 2011;37(3):525-531.

5. Y?lmaz OF, Alagöz N, Pekel G, et al. Intracorneal inlay to correct presbyopia: Long-term results. J Cataract Refract Surg. 2011;37(7):1275-1281.

6. Seyeddain O, Hohensinn M, Riha W, et al. Small-aperture corneal inlay for the correction of presbyopia: 3-year follow-up. J Cataract Refract Surg. 2012;38(1):35-45.

7. Seyeddain O, Riha W, Hohensinn M, Nix G. Dexl,AK, Grabner G. Refractive surgical correction of presbyopia with the AcuFocus small aperture corneal inlay: two-year follow-up. J Refract Surg. 2010;26(10):707-715.

8. Dexl AK, Seyeddain O, Riha W, et al. Reading Performance After Implantation of a Modified Corneal Inlay Design for the Surgical Correction of Presbyopia: 1-Year Follow-up. Am. J. Ophthalmol. Nov. 20, 2011. [Epub ahead of print]

9. Dexl AK, Seyeddain O, Riha W, et al. One-year visual outcomes and patient satisfaction after surgical correction of presbyopia with an intracorneal inlay of a new design. J Cataract Refract Surg. 2012;38(2):262-269.

10. Bouzoukis DI, Kymionis GD, Limnopoulou AN, Kounis GA, Pallikaris IG. Femtosecond laser-assisted corneal pocket creation using a mask for inlay implantation. J Refract Surg. 2011;27(11):818–820

11. Bouzoukis DI, Kymionis GD, Panagopoulou SI, et al. Visual outcomes and safety of a small diameter intrastromal refractive inlay for the corneal compensation of presbyopia. J Refract Surg. 2012;28(3):168-173.

12. Tomita M, Kanamori T, Waring GO 4th, et al. Simultaneous corneal inlay implantation and laser in situ keratomileusis for presbyopia in patients with hyperopia, myopia, or emmetropia: Six-month results. J Cataract Refract Surg. 2012;38(3):495-506.

Financial Interests

Dr. Dexl has no financial interest in corneal inlays. He is co-holder of a patent for the Salzburg Reading Desk, a tool for measuring functional changes in near acuity.

Dr. Chu is a consultant to Abbott Medical Optics and Bausch+Lomb.

Dr. Waring IV has a financial interest in and is world surgical monitor for Acufocus. He is a consultant to Topcon, Ista and RevitalVision.