March 2017

 

COVER FEATURE

 

Advances in corneal inlays
History of inlays, the current market, and what’s yet to come


by Liz Hillman EyeWorld Staff Writer

   

This early generation polysufone implant placed in 1982 by Peter Choyce, MD, of England to treat high myopia shows early vascularization. It eventually needed to be explanted.

An early generation Presbia-style hydrogel implant placed by Dr. Lindstrom in 1987. The patient is still doing well 30 years later with 20/25 at distance and J2 at near.

A patient of Dr. Lindstrom’s with an AcuFocus KAMRA inlay placed in 2015. The patient’s vision is 20/25, J1, and stable.
Source (all): Richard Lindstrom, MD

What’s available now and what’s coming down the pipeline with these presbyopia-correcting implants

Intracorneal inlays have come a long way since they were first introduced as a concept in 1949 by Jose Barraquer, MD, Barcelona, Spain.1 In the decades following, research was conducted on the effect of an implant in the cornea for correction of myopia and aphakia.2,3
New procedures would eventually supersede inlays for these refractive conditions, but the implants found their market and materials would improve to the point of being well-tolerated within the cornea.
Richard Lindstrom, MD, Minnesota Eye Consultants, Minneapolis, first started working with intracorneal inlays 30 years ago using polysulfone lenses for the correction of high myopia. While the outcomes for treating myopia were quite good, Dr. Lindstrom noted that the material prevented glucose diffusion and resulted in vascularization.
“That, however, led us to appreciate that if you’re going to use a non-permeable material, you need to microperforate it. That was great learning,” Dr. Lindstrom said.
Following that, Dr. Lindstrom said he worked with a company to develop a hydrogel intracorneal lens for the treatment of myopia and aphakia. While this showed promise at the time, it was usurped by the success of PRK and LASIK with the excimer laser.
“Then we transitioned to the idea that an intracorneal lens might be a useful adjunct for presbyopia,” Dr. Lindstrom said.
Fast forward to present day. There are two inlays approved by the U.S. Food and Drug Administration (FDA), the KAMRA inlay (AcuFocus, Irvine, California) and the Raindrop Near Vision Inlay (ReVision Optics, Lake Forest, California), and one in clinical trials leading toward FDA approval, the Flexivue Microlens (Presbia, Irvine, California). All three of these inlays have the CE mark.
“The first question patients asked eye surgeons 20 years ago was, ‘Can you get rid of my glasses, can you get rid of my contacts?’ And we could say yes when LASIK was approved,” said Ralph Chu, MD, Chu Vision Institute, Bloomington, Minnesota. “Now they ask, ‘Can you get rid of my reading glasses?’ And we can actually say yes to that now.”

KAMRA

The KAMRA, which was approved in April 2015, operates based on the principle of small-aperture optics, much like a camera or pinhole effect. Placed in a femtosecond laser-made pocket in the patient’s non-dominant eye and centered over their pupil, this opaque, porous inlay made of polyvinylidene difluoride narrows the pupil’s aperture size to increase depth of focus.
The 3.8 mm inlay with the central open space of 1.6 mm was approved for presbyopic patients with +0.5 D to –0.75 D of cycloplegic refractive spherical equivalent with 0.75 D refractive cylinder or less. According to AcuFocus, the patient should not rely on glasses or contact lenses for distance vision. Some surgeons will, however, perform LASIK in sequence with the inlay or simultaneously, said Daniel Durrie, MD, clinical professor of ophthalmology, University of Kansas, Overland Park. AcuFocus, however, notes that the safety and efficacy of this combination is not known. Dr. Durrie also said that the KAMRA seems to perform better in patients who are slightly myopic, which is something the surgeon can create to maximize outcomes.
Per AcuFocus’ Ophthalmic Devices Panel Executive Summary submitted to the FDA, 83.5% of the 478 patients included for evaluation in the pivotal study achieved uncorrected near visual acuity (UCNVA) of 20/40 or better 1 year postop.4 At 36 months, 87.1% of the 417 subjects available for evaluation achieved UCNVA of 20/40 or better. Less than 1% of subjects had induced cylinder because of the procedure, and the mean endothelial cell loss was about 5% but it stabilized by 1 year. As for subjective, patient-reported symptoms, dryness was the most common.
As with other procedures, Dr. Durrie said setting patient expectations for the KAMRA is important. While some patients see improvement in the first week, it may take 2 or 3 weeks for the majority to start experiencing the effects, with a small number taking up to 3 months. KAMRA patients might also struggle in low light situations, Dr. Durrie said.

Raindrop

The Raindrop, the latest to receive FDA approval in June 2016, is a hydrogel implant with a 32 µm central thickness placed under a LASIK flap at a depth of one-third corneal thickness, leaving at least 300 µm below the flap. The inlay steepens the optical zone to increase depth of focus. It is indicated for presbyopes with a manifest refractive spherical equivalent of +1 D to –0.5 D with adequate distance vision but requiring +1.5 D to +2.5 D of reading vision. Like the KAMRA, the safety and efficacy of the Raindrop combined with LASIK or PRK is unknown, according to the company.
Clinical trials showed this inlay can tolerate up to 0.7 mm of decentration in any direction, but Dr. Chu said he finds it more forgiving to inferior nasal placement and overall more forgiving to decentration than the KAMRA.
During the surgery, Jeffrey Whitman, MD, Key-Whitman Eye Center, Dallas, noted that the femtosecond flap should be wetted with balanced salt solution every 20 seconds to ensure it doesn’t dry out and develop striae. After the inlay is centered, has dried adequately (look for a dimpling effect like than of an orange peel), and the flap has been laid down, surgeons should expect a gutter opposite the hinge given a space-occupying implant under the flap. Dr. Whitman said this is normal and will be gone the next day.
“Don’t play with it, don’t irrigate around it, don’t think you can minimize it. Just stroke a few times when laying the flap down,” Dr. Whitman said, noting that he does place a bandage contact lens for the patient’s comfort.
What Dr. Whitman thinks is nice about the Raindrop is its similarities to LASIK.
“If I know how to do LASIK, I can do the Raindrop. I’m not learning a new technique; I have lasers that can already make a LASIK flap, and I know how to work under a flap,” he said.
However, Dr. Chu cautioned against treating inlay patients like LASIK patients completely.
“They need closer follow-up,” Dr. Chu said, recommending these patients be followed closely for the long term. “Almost all of the complications that can happen from these inlays can be avoided if the patient is followed up earlier and treated appropriately before anything serious happens.”
Initial clinical trials for FDA approval revealed 92% of patients could see 20/40 or better at near 2 years postop.5 Central corneal haze was listed as one of the most common complications (16.6%), but it resolved in 89% of subjects.
ReVision Optics is currently conducting further clinical studies on the use of the Raindrop inlay in pseudophakic patients as well as in a femtosecond laser-created pocket rather than under a flap.

Flexivue Microlens

This clear, corneal 3.2 mm inlay consists of a 1.6 mm central area with no refractive power and a peripheral ring with a refractive power ranging from +1.5 D to 3.5 D.
“The design of the inlay results in a multifocal effect that allows the patient to experience good near vision and distance vision,” Edward Manche, MD, professor of ophthalmology, Stanford University School of Medicine, Stanford, California, said of the implant currently in Phase 3 clinical trials.
Dr. Manche said he places the hydrophilic acrylic inlay in a 300 µm femtosecond laser-created pocket, using a custom mask provided by Presbia. This small temporal incision is self-sealing, and Dr. Manche said the 5- to 10-minute procedure is “completely painless.” Selecting the right power for patients is determined based on their age and functional needs for near vision.
While Dr. Manche said his patients’ experience with the inlay has been good, he noted a monovision contact lens trial helps determine the best power and patient tolerance.
According to a Presbia press announcement from May 2016, all 412 study participants in the pivotal study had completed 6-month postop visits. The company said that by the fourth quarter of 2017, it expects to have 24-month postop data on 300 patients to submit its premarket approval module to the FDA.
In August 2016, Presbia acquired Neoptics (Hünenberg, Switzerland), integrating intellectual property and know-how from the latter company’s Icolens—a bifocal, hydrogel (2-hydroxyethyl methacrylate and methyl methacrylate) implant—into the Flexivue Microlens.

What inlays bring to the market

“Everybody gets presbyopia and nobody loves presbyopia,” Dr. Whitman said. “Here’s a disease that affects everyone, so there is a huge market out there in a patient segment that should be able to afford it.”
Until the recent approval of intracorneal inlays, the only surgical option for presbyopia was monovision or multifocal IOLs at the time of cataract surgery. These implants offer freedom from readers (though there will be situations where they may still be needed) without compromising distance vision and without having to wait for a cataract to develop. What’s more, they can be removed if the outcome is not positive.
With two FDA-approved inlays on the market and a third expected, ophthalmologists differ in their opinions as to how they’ll be adopted. Some think physicians will train in all inlay types, giving them the ability to choose the best inlay for each patient’s situation. Others, however, think surgeons will choose to specialize in one and will use PRK or LASIK to tailor the patient to the inlay.
Dr. Lindstrom said while it might start with physicians choosing to work with a specific inlay, he thinks surgeons will eventually add more options.
“It’s a bit like if you look at presbyopia-correcting lenses,” Dr. Lindstrom said, noting that ophthalmologists use different types of multifocal IOLs depending on the patient. “I think this will be the same. … My group has decided, based on current volume of procedures and experience we have, that we’re going to continue doing the KAMRA for now, but that doesn’t mean we would never want to get trained in the Raindrop or Flexivue in the future.
“The bottom line is it’s too soon to know how this is going to sort out. The good news is we have two good choices of something we never had before and within a year or two we’ll have a third good choice,” Dr. Lindstrom said.

Invigorating ophthalmology

While the inlays are beginning to serve a previously untapped market, they’re also reinvigorating ophthalmologists and their practices.
“Inlays not only are great new technologies, but I think they’re firing up surgeons again to start thinking about how they can take care of these patients,” Dr. Durrie said. “Sometimes practices need a new technology, like an inlay, to get them fired up to start doing promotions, seminars, Facebook Live, and other things to get the word out that patients should come in and talk to their doctor if they’re having these issues.”
Even if the patient comes in the door and is not a candidate for an inlay, Dr. Durrie said he or she might be a candidate for another procedure to improve vision.
“These people are coming in for the inlay, but some are not great candidates. Still, you can talk to them about what they are a great candidate for. That’s why we’ve seen this real interest in practice growth,” Dr. Durrie said.

References

1. Barraquer JI. Queratoplastia Refractiva. Estudios e Informaciones Oftalmológicas. 1949;10:2–21.
2. Barraquer JI. Modification of refraction by means of intracorneal inclusions. Int Ophthalmol Clin. 1966;6:53–78.
3. Steinert RF, et al. Hydrogel intracorneal lenses in aphakic eyes. Arch Ophthalmol. 1996;114:135–41.
4. AcuFocus. Ophthalmic Devices Panel Executive Summary. FDA. 2014. Accessed Jan. 9, 2017. www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/
MedicalDevices/MedicalDevicesAdvisoryCommittee/OphthalmicDevicesPanel/UCM399644.pdf

5. ReVision Optics. Summary of Safety and Effectiveness Data. FDA. 2016. Accessed Jan. 9, 2017. www.accessdata.fda.gov/cdrh_docs/pdf15/P150034b.pdf

Editors’ note: Dr. Lindstrom has financial interests with AcuFocus. Dr. Durrie has financial interests with AcuFocus, Alcon (Fort Worth, Texas), and Abbott Medical Optics (Abbott Park, Illinois). Drs. Chu and Whitman have financial interests with ReVision Optics. Dr. Manche has no financial interests related to his comments.

Contact information

Chu: yrchu@chuvision.com
Durrie: ddurrie@durrievision.com
Lindstrom: rllindstrom@mneye.com
Manche: edward.manche@stanford.edu
Whitman: whitman@keywhitman.com