Presbia Inc.) Corneal That Never Really Got Are Talking About Inducing Monovision Try to Improve Vision

PRESBYOPIA AND CORNEAL INLAYS Corneal inlays discover new lease of life as potential presbyopic treatment by Dermot McGrath

he past few years have seen a Back to the future Given the current the inlays were eventually replaced by lasers resurgence of interest in corneal hype surrounding presbyopic inlays, it is which did the job more accurately,” he said. inlays as a potential treatment The Vue+/PresbyLens inlay (ReVision I think we need to perhaps easy to forget that the technology for presbyopia. Some surgeons has actually been around for a long time, Optics Inc), currently undergoing clinical “keep an open mind have hailed the latest generation of inlay trials in the US, uses a refined version of this T said Daniel S Durrie MD, clinical professor and not rush to technologies as a breakthrough in the search of ophthalmology, University of Kansas approach, but changes the corneal curvature judgment on this for a universally effective and universally Medical Centre, and president, Durrie in the centre of the cornea only. promising technology applicable treatment for presbyopia. Vision, Kansas, US. The second type of inlay sought to change Others warn that the marketing hype is “Corneal inlays for improving vision are the corneal power by putting a high index running ahead of the clinical reality and not a new concept. Back in the early 1980s refraction inlay in the cornea. José Güell MD that the inlay needs more hard data and we saw several different attempts at corneal “They ended up not being very permeable longer follow-up to assess its credentials as a inlays for the presbyopic market that never and the cornea biologically did not tolerate groundbreaking technology. really got off the ground for one reason or them very well, so that too was abandoned,” “I think we need to keep an open mind another,” Dr Durrie told EuroTimes. “What said Dr Durrie. and not rush to judgment on this promising we are seeing now is the maturing of this This approach has since been re-visited technology,” said José Guell MD, director technology, which addresses a lot of the by two inlays: the InVue corneal inlay Back in the early of the Cornea and Refractive Surgery Unit earlier issues with the inlays, and also more (originally developed by BioVision AG, later at the Instituto de Microcirugia Ocular, acquired by Neoptics AG) which addressed “1980s we saw several clinical data and commercial results are Barcelona, Spain. “We need more scientific the bio-compatibility issue by incorporating different attempts at starting to filter through, so we are seeing a data on both the safety and efficacy of new excitement about it,” he said. a pinhole in the centre of the lens that corneal inlays for the these inlays before we start recommending Dr Durrie identified three main types of allowed nutrients to pass through, and the presbyopic market them systematically to our patients. If we inlay that have been used over the years to Flexivue Microlens (Presbia Inc.) corneal that never really got are talking about inducing monovision try to improve vision. The first approach inlay which is placed in a self-sealing off the ground for one optionally in an otherwise healthy eye just tried to use inlays to change the corneal stromal pocket which holds the lens in place reason or another to slightly enhance near vision, then I don’t curvature, and in the process alter the in the centre of the visual axis. think the argument is strong enough to corneal power. propose that to my patients right now. But “A lot of these early attempts used Changing the optical principles Daniel S Durrie MD it could certainly be an interesting addition materials that were not very permeable to The third strategy to improve vision for to our surgical toolkit and merits close oxygen or glucose and were difficult to do presbyopes eschews changing either the attention as more data becomes available,” because everybody’s corneal curvature is power or the curvature of the cornea, but he said. different and it just wasn’t very accurate. So instead seeks to alter the optical principles

The versatility of the “Kamra inlays makes them a great solution for presbyopia

Gunther Grabner MD Courtesy of Gunther Grabner MD

EUROTIMES | Volume 16 | Issue 11 “There has been a definite shift in the age profile of the typical refractive surgery 5 patient in recent years, from around 35 years about a decade ago to around 45 or 50 years-of-age today. These patients are looking for simple and effective solutions that can take care of their presbyopia, and I think corneal inlays will give us further options to offer more personalised solutions for these patients,” she said. Compared to approaches such as PresbyLASIK or IntraCor, corneal inlays offer a minimally invasive, safe, reversible

Flexivue Micro-Lens Corneal Inlay (Presbia) surgical technique for presbyopes, said Dimitris I Bouzoukis MD, Institute of Vision and Optics, University of Crete, Greece “There is no steep learning curve for the surgeon and the surgery can be performed without changing or adding new equipment or software in a modern refractive surgery theatre equipped with a femtosecond laser,” he said.

Downsides to inlay technology But even the best technology has its IntraCor technique downsides – and corneal inlays are no Courtesy of Albou-Ganem MD exception. FLEXIVUE MICRO-LENS Inlay Characteristics: “The main disadvantage is that the inlay – Acts changing the refractive index of the cornea – Biocompatible hydrogel-based material with a central hole to increase more the nutrient flow. is a reasonable but not a perfect solution for – Donut shape bifocal refractive power presbyopia, as only one eye is corrected,” – The refractive effect is pupil depended, inreasing during – The lens is implanted into the stroma of the cornea on the said António Limão Oliveira MD, Instituto non-dominant eye, inside a corneal tunnel created using near vision and decreasing during far vision, femtosecond laser. changing less the far vision in the operated eye than in a Microcirurgia Ocular in Lisbon, Portugal, classic monovision procedure – The lens is “Invisible” who has been involved with the European The reversibility

Courtesy of Dimitris I Bouzoukis MD multicentre trial of the Vue+ corneal inlay. “With this approach, binocularity “factor is certainly is disturbed, at least at near, and patients very attractive. If the of the cornea using small aperture optics. “The reversibility factor is certainly very become independent but not completely patient doesn’t like This is the approach favoured by the attractive. If the patient doesn’t like them, free of glasses for near vision,” he said. In them, they can be Dr Oliveira’s view, the best candidates for Kamra inlay (previously the ACI 7000, they can be easily removed and no further easily removed and inlays are emmetropic presbyopes with a AcuFocus Inc.), which is leading the inlay procedure is required to restore them back no further procedure pack in terms of regulatory approval and to their original refractive status. I also clear lens, 20/20 uncorrected distance vision is required to restore clinical follow-up, with over 5,000 implants appreciate the fact that the inlays always and a near add of about +2.00 D. performed worldwide and four-year data enhance near vision, with only a marginal “The most important exclusion criteria them back to their from a Turkish centre now published1. loss of distance acuity depending on the for the Vue+ corneal inlay is dry eye, any original refractive “The versatility of the Kamra inlays makes inlay utilised. Because it is a monocular kind of corneal pathology, central corneal status them a great solution for presbyopia,” procedure, you always maintain quality thickness inferior to 500 microns, and monovision intolerance,” he said. said Gunther Grabner MD, professor distance vision in the other eye, which the Richard Lindstrom MD of ophthalmology and chairman of the patients seem to appreciate,” he said. Inlays may also be unsuitable for patients University Eye Clinic at Paracelsus Medical with very high expectations, said Dr University in Salzburg, Austria, noting Target market In Dr Lindstrom’s Bouzoukis. “As with all bifocal or multifocal that they have been implanted successfully view, the real target group for inlays are corrections, retinal image contrast may be in emmetropes, ametropes, monofocal not so much early-stage presbyopes that reduced in eyes implanted with the Flexivue pseudophakic patients and post-LASIK occasionally need reading glasses, but rather and Vue+ devices and retinal illuminance patients. the presbyopic population aged around may be markedly reduced with the Kamra There has been a “In the United States clinical study 50-upwards who have become handicapped implant. Effects on contrast sensitivity and stereopsis have yet to be adequately “definite shift in the of 507 patients who received the Kamra enough in their daily activities to consider inlay, 18-month data showed that the inlay alternatives to reading glasses. explored. Regarding reversibility and safety, age profile of the provided patients, on average, with J-2 While the initial expectation in the more studies are needed to demonstrate if typical refractive uncorrected near acuity, 20/25 uncorrected industry was that corneal inlays would hold the technique is really reversible with no surgery patient in changes to the preoperative emmetropic intermediate acuity and 20/20 uncorrected most appeal for emmetropic presbyopes, the recent years, from status of these patients, or if they are just distance acuity in their inlay implanted reality on the ground has been somewhat around 35 years eye. Additionally, for the Kamra inlay, the different, he said. removable, and to demonstrate that after a about a decade ago mechanism of action using small aperture “Emmetropic presbyopes are certainly long follow-up they are not creating corneal optics continues to work over several years candidates but the largest number of alterations,” he said. to around 45 or 50 without a reduction in acuity, as can happen patients who seem to ask for the surgery Prof Grabner said that in his clinical years-of-age today with other power-based corneal inlays that are presbyopes who are also myopic or experience with the Kamra inlay, there was no significant reduction found in retinal need to be updated as the patient’s lens hyperopic and may also have astigmatism. Cati Albou-Ganem MD continues to lose accommodative function,” I see those patients in my practice every illuminance for patients implanted with he said. day, but understandably they don’t want to the inlay, and he believes that the five-year The inlays are also removable, allowing trade far glasses for near glasses. For these follow-up data speaks volumes for the long- the patient to take advantage of future patients, the best solution is usually what term safety of the device. technologies for correcting presbyopia or we call SIM-LASIK, which is LASIK first to “We tested the inlay and found that there cataract should the need arise, added Prof correct their ametropia and then the inlay to was only a very slight reduction in the mean Grabner. deal with their presbyopia,” he said. deviation visual field of 2 dB. We now have As a selling point for inlay technology, While the demand for presbyopic up to five years' follow-up in the first series the implant’s reversibility should not be treatments worldwide is on the increase, – a time frame that seems quite reasonable underestimated in a competitive market, patients today are much better informed to postulate that they are very safe,” he said. according to Richard Lindstrom MD, about the options open to them, said Cati Another potential problem is that not all founder of Minnesota Eye Centres, Albou-Ganem MD, in practice at the patients adapt quickly to their post-inlay Minneapolis, US. Clinique de la Vision, Paris, France. vision, said Dr Albou-Ganem. “I recently

EUROTIMES | Volume 16 | Issue 11 José Güell - [email protected] Daniel Durrie - [email protected] 6 Cover Story Gunther Grabner - [email protected] Richard Lindstrom - [email protected] Cati Albou-Ganem - [email protected]

PRESBYOPIA contacts Dimitris Bouzoukis - [email protected] António Limão Oliveira - [email protected]

There is no steep “learning curve for the surgeon and the surgery can be performed without changing or adding new equipment or software in a modern refractive surgery

theatre equipped with Courtesy of António Limão Oliveira MD a femtosecond laser (1) Slit lamp photo of a Vue+ inlay well centred in the pupil (2,3) Animated eye representing the Vue+ inlay

Dimitris I Bouzoukis MD did a LASIK procedure followed by Kamra but believes that an electronic alignment for a little residual myopia in the inlay eye implantation in the non-dominant eye of system such as that recently introduced for and use the AcuTarget-System to place the a myopic patient but after several days the the Kamra inlay, effectively deals with this Kamra inlay with great precision,” he said. patient was still not very comfortable with issue and will become the norm for optimal it. However, I always urge these patients placement of these types of implant. Massive market potential While to give it time because there is a process Using latest-generation femtosecond corneal inlays are still only in the early of neuro-adaptation with the inlay. It is a laser technology will also help to reduce phases of adoption for most ophthalmic The main little bit like the IntraCor procedure in this variations in wound healing, said Dr Durrie. practices, that picture could change “disadvantage is respect – some patients have immediate “We found that creating the femtosecond rapidly as more clinical trial data becomes that the inlay is a results after the surgery, but sometimes it pocket or flap atraumatically using the available and demand for the inlays gathers reasonable but not a takes a few weeks for other patients to adapt latest laser models resulted in faster visual momentum. perfect solution for to their new vision,” she said. rehabilitation. The key is making sure “From a business aspect, this appears to Centration is another potential issue that you are using modern equipment for be one of those rare products that turns presbyopia, as only with inlays, said Dr Lindstrom, and some a smooth ablation and then there is less out to be a win-win-win situation for one eye is corrected concerns have also been raised about long- variability in the wound healing,” he said. the patient, the doctor and the company term bio-compatibility. “There can be some For optimal outcomes with the producing it,” said Dr Durrie. “It is António Limão Oliveira MD mild interface reaction that occurs between Presbylens/Vue+ inlay, Dr Oliveira advised relatively straightforward for the company the implant and the cornea. I have seen using disposable instruments, with careful to produce, and patients tend not to mind some earlier generation hydrogel inlays delivery of the inlay in the centre of the spending a bit more money on it in order 20 years after implantation and they look pupil, without tearing it, and keeping the to get what they consider to be a top-of- good with no visually significant scarring. flap hydrated to avoid microstriae, he said. the-line product. As doctors, we are often But if you remove the inlay and look very Prof Grabner highlighted the importance introduced to technologies that just increase carefully you can see where the implant was of managing patient expectations and the cost of what we are doing without really placed. That occurs with the Kamra inlay advised careful and aggressive management increasing the value, which is definitely not as well, although it does not cause visually of dry eye pre- and postoperatively, as this the case with corneal inlays,” he said. significant light scatter or other symptoms,” population tends to have drier eyes. “Other he said. tips to get the best from the Kamra inlay [1] Ömer F. Yılmaz, et al. Journal of Cataract & Refractive Surgery Vol. 37, Issue 7, Pages 1275-128. Dr Durrie agrees that centration is are to ensure that patients follow the post- critical for optimal functioning of the inlay, op medication regimen precisely, to target

INLAY COMPANY PHYSICAL PROPERTIES Mechanism of action Regulatory situation

Kamra AcuFocus 3.8mm diameter, opaque biocompatible polymer The inlay’s 1.6mm centre aperture creates a CE mark. FDA trials nearing completion Inc. material, a 1.6 mm centre aperture and 8,400 pinhole effect which is designed to improve random holes for oxygen and nutrition flow. depth of focus, allowing the eye to see near and Implant placed under corneal flap or in corneal intermediate objects more clearly pocket using proprietary guidance system

InVue BioVision 3.0mm diameter and 15 µm to 20 µm thick The centre of the lens has no power, but features Technology acquired by Neoptics AG. Trials AG microlens made of hydrophilic acrylic material a pinhole for nutritional purposes. Near vision is currently under way in Europe corrected by the lens’ outer rim

Vue+ ReVision 2.0mm diameter bio-engineered, Adds a microscopic change in curvature to the CE mark. FDA trials currently under way in the Optics Inc. micro-porous, hydrogel material centre of the cornea of non-dominant eye to add United States near and intermediate focusing power

Flexivue Presbia 3.0mm diameter refractive hydrophilic polymer The lens’ central zone is free of refractive power CE mark Microlens Coöperatief lens placed in a corneal stromal pocket using with a standard positive refractive power in the U.A. FS laser peripheral zone

Don’t miss Paediatric Ophthalmology, see page 37

EUROTIMES | Volume 16 | Issue 11