Corneal inlays provide safe, reversible option for presbyopia treatment

In the United States, two different corneal inlays for the treatment of presbyopia are undergoing U.S. Food and Drug Administration clinical trials.

The first, the Kamra corneal inlay (AcuFocus), creates a pinhole effect to increase depth of field. The second, PresbyLens (ReVision Optics), is a hydrogel implant that is placed beneath a stromal flap, where it alters the anterior corneal shape.*

Corneal inlays for the treatment of presbyopia offer an example of how perseverance and trial and error can lead to success.

José Barraquer pioneered the idea of implanting a lens intracorneally. In 1949, he developed the first prototype, which was soon abandoned because of the corneal tissue’s aggressive response to the flint glass material.

Two decades later, the discovery of hydrogel polymers led researchers to revisit the concept of corneal inlays. The new materials were transparent and permeable to nutrients and promised to be well-tolerated by the corneal tissue. However, complications such as corneal opacification, thinning and melting still occurred. Less expected were the effects on vision, with decentration and haze impairing results and visual loss occurring over time.

“There was a long way to go before biocompatibility issues were resolved,” Alain Saad, MD, an ophthalmologist at Fondation Ophtalmologique Adolphe de Rothschild in Paris, said. “It was not just the material itself to cause metabolic problems, but also the thickness of the inlay and the depth at which it was implanted.”

Miscalculations in inlay thickness and implantation depth led to flap thinning because the inlay blocked nutrient flow to the anterior stroma and epithelium.

“The first inlays were more than 15 µm thick, and there was no perception that inlays had to be placed deep into the cornea at an optimal depth to allow nutrient flow and corneal tolerance,” Minoru Tomita, MD, PhD, an ophthalmologist at Shinagawa LASIK Center in Tokyo, said.

Kamra corneal inlay

The Kamra corneal inlay is currently the most widely used inlay, with more than 15,000 implantations performed globally. Over the years, it has undergone improvements, including six design changes. Increasingly biocompatible materials were developed, and optimal depth placement has been evaluated by several studies.

“We now use the latest model, ACI 7000PDT, which is made of polyvinylidene fluoride and nano-particles of carbon, with a 3.8-mm outer diameter and a 1.6-mm central aperture,” Tomita said. “It is 5 µm thick and has 8,400 femtosecond-created micro-perforations varying in size from 5 µm to 11 µm diameter to allow for nutrient flow through the cornea. The micro-perforations allow for a 5% light transmission rate through the inlay into the eye.”

“The large 1.6-mm central hole, which is unique to this inlay, contributes greatly to maintain the physiological supply of nutrients in the whole cornea,” Saad said.

Tomita and colleagues at the Shinagawa LASIK Centers have implanted nearly 10,000 Kamra corneal inlays since 2009. On average, patients achieved distance visual acuity of 20/20 and near visual acuity of J2. More than 90% of presbyopic patients in his practice receive Kamra inlays. Patient satisfaction is high, with 94% of patients happy with results and 93% not needing spectacles for reading, he said.

Saad and colleague Damien Gatinel, MD, have 2 years of follow-up for patients implanted with Kamra inlays, 95% of whom do not need glasses.

“Kamra is now our procedure of choice for presbyopic patients. It is the safest, least invasive and most effective option so far,” Saad said.

How it works

The Kamra inlay is implanted in the nondominant eye and employs the pinhole effect to increase depth of field. The small opening in the center of the implant allows only focused light to reach the retina, improving near and intermediate vision with minimal impact on distance vision.

The inlay is placed at a depth of 200 µm, using the femtosecond laser to create a flap or pocket into which the inlay is inserted.

“The femtolaser allows us to make pockets at a precise location in the cornea. New technologies such as the OPD scan (Nidek) and the AcuTarget System (AcuFocus) enable accurate centration of the implant in between the pupil center and the Purkinje reflex,” Saad said.

The inlay can be implanted quickly and easily, according to Saad. The procedure is reversible, but only 1.6% of patients require explantation, usually due to poor adaptation to the new visual system, he said.

Tomita said that it presents fewer risks than other procedures for presbyopia, such as LASIK or refractive lens exchange. It is also not dependent on age-related refractive changes and therefore is theoretically a permanent procedure.

“Kamra has no refractive power, and patients will not need to replace it as they get older,” he said.

In ametropic patients, the majority of presbyopes, it can be combined with LASIK.

“LASIK is performed first, and then the Kamra inlay is implanted,” Tomita said.

It can also be combined with cataract surgery and monofocal lens implantation to provide reading vision, according to Saad.

“Indications are very broad. Also, patients who previously had LASIK and become presbyopic can benefit from this option,” he said.

There are few limitations to the use of this technology. Dry eye may sometimes be a problem, although it tends to mitigate with time.

“If the problem persists, a punctum plug can be implanted in the Kamra-treated eye,” Tomita said.

Some patients might have problems with adaptation to near monovision as opposed to distance binocular vision.

“Neuroadaptation differs amongst individuals, and we cannot predict who is incapable of tolerating the implant at the preoperative stage. However, after the Kamra surgery, we encourage and recommend patients to perform the eye exercise, which enhances faster neuroadaptation,” Tomita said.

Saad said longer follow-up is needed to determine the best indications for the corneal inlay in order to provide the most satisfactory results for patients.

PresbyLens, Vue+

A second option is designed to improve near and intermediate vision by microscopically changing the curvature of the cornea. Produced by ReVision Optics, it is available as PresbyLens in the U.S. and Vue+ in Europe and other parts of the world. ReVision Optics will debut a product enhancement at the European Society of Cataract and Refractive Surgeons meeting in Milan, Italy.

“The PresbyLens is a proprietary hydrogel that is only 2 mm in diameter. The convex shape results in adding plus power to the central cornea. The draping of the corneal flap over the implant creates a blended transition zone over a wider diameter than the inlay itself,” Roger F. Steinert, MD, OSN Cornea/External Disease Board Member, said.

The inlay has been refined over several years. It is implanted in the nondominant eye, under a stromal flap, using a proprietary delivery system.

“One of the advantages is that the inlay can be combined with LASIK in myopic or hyperopic patients, under a freshly cut flap or a pre-existing flap,” Steinert said.

The flap is recommended to be performed with the assistance of a femtosecond laser, according to Enrique Barragan, MD, an ophthalmologist at Laser Ocular Hidalgo in Mexico.

“There is a different level of accuracy in obtaining the flap thickness you want, which is 150 µm. We do ultrasonic pachymetry to make sure we achieve exactly that thickness. A good lubrication and 150-µm thick flaps performed with femtosecond laser will avoid flap thinning problems,” he said.

Barragan has implanted 450 Vue+ inlays over 7 years and is satisfied with the results. He said patient selection is the key to success, and he offers the Vue+ only to what he terms a good candidate for the procedure. This patient will have a pupil size between 3 mm photopic and 5.5 mm mesopic and no larger than 7 mm, no dry eye issues, a preoperative keratometry reading of 47 D for emmetropes, and a predicted keratometry reading of no more than 47 D in the case of a combined LASIK procedure.

“Right from the beginning, I have wanted all my patients to be potentially successful,” Barragan said. “In the first 3 years, I implanted no more than one to three patients per month, and as I gained confidence, I went up to eight to nine per month. I don’t care about high numbers, but I want happy patients. It’s good to see that 75% of our Vue+ candidates are referred by those who had the treatment.”

Because it is power-neutral, the 30-µm inlay is suitable for all eyes of patients 46 years and older, with no need to replace it in the face of age-related refractive changes, he said.

The visual results based on international use and the FDA trials are positive, Steinert said.

“The vast majority of patients have modest reduction of distance vision in the inlay eye, much less than one would expect, averaging eight letters or 1.5 lines. That eye will simultaneously gain near vision at dramatic levels, often to the 20/20 equivalent. With binocular vision, most patients are 20/20 and J1,” he said.

Patients who maintain a good distance vision of at least 20/25 in the eye where the inlay is implanted, as well as in the fellow eye for further improvement of near vision, are good candidates for the implantation of the Vue+, Barragan said.

“It is the only inlay that, given certain conditions, can be implanted bilaterally,” he said.

Barragan is now starting to implant the Vue+ in pseudophakic patients.

“Results seem very good,” Barragan said. “The way to go, from now on, is to perform the IOL calculation prior to implanting the inlay in patients who are in their mid-40s. If a cataract occurs later in life, we can use the IOL calculation we did previously, implant the IOL targeting for plano, and the patient will be distance and near happy.”

Potential complication

Haze is the main potential complication. Steroids are administered routinely for 1 month in a tapered 4-3-2-1 fashion over a 4-week period.

“Improved purity of the inlay and a new drug regimen have dramatically reduced the incidence of haze over the last 3 years,” Barragan said. “We are close to 12% haze after implantation. If haze occurs, an additional 1 month of steroids is administered in the same tapered fashion as prescribed immediately after surgery. Following this second round of steroids, haze is reduced to 2% to 3%, and if it persists, the inlay may be removed.”

If the inlay has to be removed, the procedure is easy and safe, he said.

“You don’t even need to lift the entire flap. Simply lift the flap until you achieve access to the inlay for removal. After removal, the patient’s vision will return to its preoperative acuity within a few days to weeks,” he said.

Flexivue

The Flexivue Microlens corneal inlay (Presbia) is based on a different principle. It is a 3.2-mm diameter lens with a 15-µm edge thickness and it is made of a hydrophilic polymer. The central neutral-power zone of the lens provides a focal point for distance vision, while the peripheral positive-power area is used for near vision.

“Placed in the nondominant eye, Flexivue provides what I call ‘smart monovision.’ The near vision gain is remarkable, while the far vision loss is minimal,” Ioannis G. Pallikaris, MD, PhD, OSN Europe Edition Editorial Board Member, said.

Pallikaris, who is medical director of Presbia, has implanted the Flexivue Microlens in his practice at the Institute of Vision and Optics of the University of Crete in Greece. The lens was previously implanted under a mechanically performed tunnel, but now the tunnel is created with a femtosecond laser.

“The cut is now very precise and we can generate a very small tunnel, pocketing the cornea with a no-touch procedure,” he said. “Then, it’s very easy to insert the lens in no more than 1 minute. No special skills are needed, everything is done by the femto, guided by dedicated software.”

The patented Presbia inserter tool has been developed and is in use as part of Presbia’s Microlens solution. The inlay is loaded into the inserter and then implanted into the corneal pocket created by the femtosecond laser.

Results

Following an initial study in which 50 patients were successfully implanted through a mechanically performed tunnel, a new randomized, multicenter, prospective trial was conducted on 64 emmetropic patients implanted with the Flexivue Microlens using a 150-kHz femtosecond laser. All patients have reached 12 months of follow-up, and a subgroup has reached 3 years.

“Results are very promising,” Pallikaris said. “Visual acuity improved by six lines on the ETDRS chart. On average, patients improved from 20/100 to 20/25 on the Snellen chart. The majority of them, about 92%, are completely independent from spectacles, and the remaining 8% use spectacles 50% of the time for near tasks.”

In the operated eye, patients lose about one line of distance vision, which is not noticeable if they learn to use their binocular vision correctly. With monovision-based methods, the gap between near and far vision is much greater, leading to problems with neuroadaptation.

“With Flexivue, patients only need a short period of adaptation. Most of them have an almost immediate ‘wow’ effect, while a few are initially disappointed because they keep looking through the operated eye while closing the other eye,” Pallikaris said. “They are the ones who call me and say their vision has worsened. I fix an appointment for them to have the lens explanted in the following month. They relax, start using both eyes, and 1 month later, they call and say their vision is great and they no longer want to be re-operated.”

Combining the Flexivue Microlens with other procedures, such as cataract and laser refractive surgery, is also possible in ametropic presbyopes.

“We correct the refractive error, hyperopia or myopia, first, and then we address presbyopia with the inlay,” Pallikaris said.

As presbyopia progresses, the lens might need changing for a higher refractive power. There is no problem in these cases, because the Flexivue Microlens is easy to explant and replace with a lens with a different power without affecting the cornea. Also, the inlay can provide multifocal vision in addition to monofocal IOL implantation in patients who need cataract surgery.

“It is an easier way of obtaining multifocality. Compared to multifocal IOLs it requires less adaptation and has the advantage of being a reversible procedure. Explanting a multifocal IOL, which happens in about 7% of the cases, carries the risks that we all know very well. Explanting a Flexivue lens is easy and safe,” Pallikaris said.

Because the Flexivue Microlens is a transparent inlay, it has the additional advantage of not needing to be removed in the event of a future femtosecond laser-assisted cataract procedure because it will not interfere with the laser beam, he said.

“Transparency also allows observation of the ocular fundus and means that the lens is invisible to observers, resulting in perfect cosmetic appearance,” Pallikaris said.

Outside the study, Pallikaris has implanted the Flexivue Microlens inlay in about 250 additional patients.

Safe, reversible options

For the three inlays, the ideal patient age is between approximately 45 and 65 years, according to all surgeons interviewed.

“These are the patients who could be considered too old for presbyopia corneal surgery and too young for lens extraction,” Pallikaris said.

“The ideal patient for Kamra inlay would be someone who is over 45 years old, is presbyopic but has not developed cataract yet,” Tomita said.

“Potentially, they could be implanted also at an older age and are not incompatible with cataract surgery. But older patients may have dry eye issues that make inlays contraindicated,” Saad said.

All surgeons interviewed perform other procedures for presbyopia but find inlays the best option and offer them to upwards of 80% of patients seeking presbyopia treatment.

“The greatest advantage of this technology compared to other methods of presbyopia correction is that it is 100% reversible,” Pallikaris said. “Removing or replacing an inlay is easy and safe. Vision goes back to normal, and there are no consequences.” – by Michela Cimberle

*See the blog “Why presbyopic corneal inlays will change the future” by John A. Hovanesian, MD, FACS, posted on June 20, 2012, at Healio.com/Ophthalmology.

Considering the differences in material, size and mechanism of action between the two corneal inlays under study in the US, what is your procedure of choice and why?

Kamra inlay offers broad focal range, nutritional pores

The Kamra inlay (AcuFocus) is furthest along in the regulatory and developmental pathway, with more than 15,000 Kamra inlays implanted worldwide, eight of which have been implanted in ophthalmologists. This inlay represents a new paradigm in refractive surgery and has many distinct advantages. The small aperture functions like the f-stop of a camera, providing a robust depth of focus and excellent acuity at near, intermediate and distance in the implanted eye. Due to the mechanism of action, this broad focal range is resistant to the progressive nature of presbyopia, which is unique to corneal presbyopic surgery and allows for stable near vision over time. The metabolic, catabolic and hydration pathways are preserved through 8,400 nutritional pores. The Kamra is a flexible technology and can be combined with other refractive procedures, including LASIK, or utilized after refractive procedures such as previous LASIK, CK or IOL implantation. Given the opaque nature of the inlay, it is easily located in the rare event when a patient may elect to have the inlay removed.

George Waring IV, MD, is the director of refractive surgery at the Medical University of South Carolina’s Storm Eye Institute and is the medical director at the Magill Vision Center. Disclosure: Waring is on the medical advisory board and is a consultant for AcuFocus.

PresbyLens offers high-quality vision, ease of use, patient satisfaction

Having used the PresbyLens (ReVision Optics) in the FDA study and also speaking to others who have used the AcuFocus Kamra inlay out of this country and having read about its use, here are my thoughts.

PresbyLens produces a more prolate cornea, which provides a multifocal effect that better utilizes light transmission at all distances. Kamra works by a pinhole effect.

PresbyLens provides near vision immediately after the surgery, with the focus point improving over the first few weeks. Kamra can take months to achieve its full near vision quality.

PresbyLens is essentially invisible to anyone looking at the patient’s eye and may not even be easy to see on cursory slit lamp observation. Kamra is more easily visible and may stand out as a black-like ring on light color irides, and iron rings or deposits can develop after the first few years after implantation.

PresbyLens is a hydrogel material with almost 80% water content, which means that it is very biocompatible. Kamra has more than 8,000 holes to allow for diffusion of nutrients.

Kamra may have better distance vision due to the pinhole effect, but binocularly both Kamra and PresbyLens should give similar uncorrected distance vision.

Lastly, PresbyLens’ effect is not bothered by decentration within ±0.5 mm of the pupil center, making placement straightforward under the operating microscope with a constricted pupil. Kamra is centered on an estimation of the visual axis using the Purkinje reflection method, and placement is more critical and can be more difficult.

In summary, having used PresbyLens for the past year, I find the quality of vision, ease of use and patient happiness factor to be very high. When both are available in the United States, more comparisons will be possible to help all of us improve our clinical and surgical practice.

Jeffrey Whitman, MD, is an OSN Cataract Surgery Board Member and president and chief surgeon at Key-Whitman Eye Center in Dallas. Disclosure: Whitman is an investigator in the PresbyLens clinical trial but has no financial interest in ReVision Optics or AcuFocus.