Consultants discover CAIRS by means of landmarks that formed its evolution


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Corneal allogenic intrastromal ring segments, or CAIRS, have been gaining momentum over time as a minimally invasive process for treating keratoconus and corneal ectasia.

“CAIRS is a kind of mid-peripheral, mid-stromal additive lamellar keratoplasty. Nonetheless, not like different keratoplasties and even not like all different remedies for keratoconus, CAIRS is a really high-reward, low-risk surgical procedure. Only a few procedures have that profit, and the educational curve could be very easy,” Soosan Jacob, MS, FRCS, DNB, mentioned.



Courtesy of Soosan Jacob, MS, FRCS, DNB

Courtesy of Soosan Jacob, MS, FRCS, DNB

In 2015, Jacob developed the CAIRS approach and has since launched a number of refinements, designed the devices to carry out it and noticed it turn into progressively widespread globally, inspiring colleagues to introduce variations.

“I’m very comfortable in regards to the quantity of analysis and improvement that’s taking place as a result of everyone seems to be making an attempt to advance the sphere, which is able to in the end end in everyone’s profit,” she mentioned.

From first thought to custom-shaped tissue segments

Jacob considered CAIRS as a technique to overcome the issues in treating sufferers with keratoconus, be it the issues of PMMA ring segments, which she had been utilizing beforehand, or the difficulties related to deep anterior lamellar keratoplasty.

“Within the case of artificial ring segments, that they had an impact, and the sufferers have been comfortable initially, however fairly a couple of of them got here again with issues,” she mentioned. “At the moment, I used to be working with allogeneic tissues, and the 2 concepts I had have been presbyopic allogenic refractive lenticule (PEARL) for the remedy of presbyopia and CAIRS for the remedy of keratoconus.’”

Jacob quickly developed the devices to chop and insert the donor tissue, determining the channel dimension and depth, the situation, the quantity of hydration, in addition to the arc, form, thickness and quantity of the segments.

“We quickly realized that the mechanism of motion was totally different from artificial rings that work by stretching the cornea,” she mentioned. “CAIRS work by quantity enlargement and required a very totally different nomogram. In 2017, we began by customizing the arc size, the thickness, the optical zone and the depth of implantation. This was good, however there was nonetheless one thing lacking. We have been utilizing broadly comparable rings to deal with several types of keratoconus sufferers. However keratoconus sufferers fluctuate wildly even inside the identical phenotype, so how might comparable arc lengths and thicknesses work for several types of cones? So, 1 yr later, we personalized them even additional by {custom} shaping them, taking a look at particular person, small variations inside the cone of every eye, even in the identical affected person.”

Customized-shaped CAIRS confirmed a greater potential to regularize the cornea, recenter the cone and enhance imaginative and prescient. Jacob makes use of the Jacob nomogram for {custom} shaping. She can also be engaged on releasing software program that may quickly permit {custom} shaping of CAIRS to be out there to all surgeons.

“I’m very curious about working with eye banks to permit them to supply custom-shaped CAIRS to their surgeons, able to implant,” she mentioned. “Presently, I accomplice with Lions World Imaginative and prescient Institute and Great thing about Sight however would love to supply the advantages of this process to sufferers worldwide by means of extra eye banks.”

Guide methodology

In 2020, when Jacob utilized for a patent for CAIRS, she was the one one to make use of the segments and included in her software all of the choices she might envisage, together with alternative ways of chopping and preserving the segments, handbook and femtosecond dissection, and the usage of cross-linking. She tried all these totally different choices, however her conclusion was that the handbook approach, with the devoted trephine she had designed, was nonetheless the most effective for a very personalized process.

“In a dwelling eye, you may obtain excessive precision with the laser, however cadaver eyes behave otherwise and will have edema and totally different ranges of hydration. Whenever you use a femtosecond laser on a cadaver eye, you don’t have the identical degree of accuracy, actually no extra as in comparison with a trephine. That is due to variable hydration, lack of centration guides and infrequently not going full thickness,” Jacob mentioned.

The femtosecond laser can also be an added value and is extra time-consuming as a result of it requires setting all of the parameters, coming into them into the machine and making use of the suction.

“With the handbook process, after eradicating the epithelium and endothelium, I merely press down the trephine to acquire the ring of tissue after which put the customization marks and lower alongside the marked factors with a 15° blade. It takes me about 1 minute to take action,” Jacob mentioned.

As well as, the femtosecond laser poses some limitations when it comes to the shapes that may be lower, she mentioned.

“It can’t lower all of the shapes that I’m able to lower manually, precisely tailor-made to the affected person,” she mentioned. “There’s numerous calculation concerned to have the ability to get a lower at a sure angle, a sure thickness, after which abruptly change the form to a different angle. It requires numerous enter into the machine. Possibly sooner or later a few of these issues can be overcome, and I’m at present additionally working with a femtosecond laser firm making an attempt to take action.”

One other downside Jacob sees is that procedures which might be the identical as CAIRS are being launched as new procedures and with new names, resulting in confusion in terminology amongst each sufferers and surgeons alike.

“One such instance is CTAK, which was began as a round disc positioned right into a corneal pocket to deal with keratoconus,” she mentioned. “It later developed into CAIRS, which was partly personalized for size and thickness alone, was femtosecond lower utilizing a nomogram and was sterilized. These three properties have been, nevertheless, already extensively out there with CAIRS on the time, together with exact customization and {custom} shaping as a result of CAIRS was being utilized around the globe for a few years. CTAK is partially personalized CAIRS with out the benefits of {custom} shaping. Nonetheless, there’s widespread confusion that it’s a new sort of approach to deal with keratoconus that’s totally different from CAIRS. Labeling it as one thing totally different may cause critical confusion and mislead sufferers and even surgeons, as already seen taking place.”

Prolonged dehydration and femtosecond laser

Shady Awwad, MD, was instantly attracted by the CAIRS approach when Jacob introduced it in 2017 on the Indian Intraocular Implant & Refractive Surgical procedure assembly.

“A couple of months later, I had an off-the-cuff assembly together with her and Amar Agarwal and made the choice to introduce CAIRS in my follow,” Awwad mentioned. “In Lebanon, keratoconus is very prevalent, so I handled numerous sufferers, and in 2020, I launched some modifications within the approach to make insertion simpler.”

By dehydrating the segments for just a little greater than 1 hour earlier than the beginning of the process, Awwad made them inflexible sufficient to be held and inserted with out dropping form. He initially referred to as this system “corneal jerky” after which “prolonged dehydration.”

“They get laborious however pliable, like a biopolymer, and just a little bit thinner, and we implant them in a normal-sized tunnel the place they rehydrate after irrigation of the attention with balanced salt answer,” he mentioned.

One other pivotal change he launched was the event of devoted software program for chopping the segments utilizing a femtosecond laser.

“I had the thought of utilizing the laser proper from the beginning, however on the time, Ziemer was not ,” Awwad mentioned. “In the meantime, Bader Khayat in Germany and David Gunn in Australia began utilizing the laser, however with out devoted software program, the process was lengthy and cumbersome, and it was not attainable to supply uneven, personalized segments.”

In 2021, Fabian Müller, an engineer at Ziemer, approached Awwad and embraced his mission. Collectively, they developed software program for chopping uneven allogenic segments utilizing a femtosecond laser, and so they fine-tuned the process and began scheduling sufferers, acquiring good outcomes.

“Uneven segments have been on high of my checklist to deal with sure phenotypes of keratoconus like snowman and duck wherein the astigmatism doesn’t align with the coma,” Awwad mentioned. “By utilizing the normal uniform segments, you would possibly flatten the cone and enhance coma however on the expense of accelerating dramatically the astigmatism. Asymmetrical segments are good to deal with these phenotypes that we see in 7% to 10% of sufferers.”

The femtosecond laser process has an extra value, and Awwad shouldn’t be utilizing it in all his sufferers.

“The femtosecond process shines in chopping asymmetrical segments since you want that sort of precision,” he mentioned. “If you wish to lower simply common segments — that’s 90% of what you do, truthfully — mechanical chopping continues to be an awesome alternative, and it’s cheaper. However femto is there, and we wish to proceed pushing it as a result of that’s how innovation begins.”

ECO-CAIRS with cross-linking

“When Shady Awwad translated Soosan Jacob’s CAIRS to the femtosecond laser, we began introducing the process on the ELZA Institute,” Farhad Hafezi, MD, PhD, mentioned. “Ziemer is 1 hour away from us, and my colleague Emilio Torres-Netto had earlier expertise with PMMA rings.”

Hafezi launched one more variation to the process as an alternative choice to Awwad’s prolonged dehydration. To make insertion simpler, and on the identical time remove any danger for an infection and rejection, Hafezi utilized a modified cross-linking approach to the donor.

Farhad Hafezi, MD

Farhad Hafezi

“I used to be additionally involved in regards to the likelihood of implanting tissue from a donor with keratoconus, and the reply was cross-linking,” he mentioned. “My pal Cosimo Mazzotta had the identical thought, even earlier than us, however what we developed was a particular nomogram with 10 instances the conventional vitality. Since you are exterior the human physique, there’s nothing you may hurt, and the corneal tissue turns into as stiff as a bit of plastic, very simple to implant and sterile.”

An extra benefit is that the cross-linked segments don’t swell throughout insertion however swell step by step, inside a couple of days after the process. This enables for the insertion of no matter quantity of quantity is required for the person cornea.

“OCT elastography measurements confirmed us that it’s the quantity to supply the flattening impact, and in some instances, we’d must insert a giant quantity right into a tiny tunnel,” he mentioned.

Hafezi referred to as this technique ECO-CAIRS, quick for “extracorporeal optimization of corneal allogenic intrastromal ring segments.”

Elastography research

Some years in the past, Emilio Torres-Netto, MD, PhD, carried out his first elastography research on PMMA rings to know their biomechanical results on the cornea and probably optimize their efficiency.

Emilio Torres-Netto, MD, PhD

Emilio Torres-Netto

“We’ve totally different nomograms in line with the producers, and precision and predictability should not so excessive as we wish in refractive procedures. We regularly have surprises after implantation,” he mentioned.

In considered one of these research, segments with arc size of 120°, 210° or 325° have been implanted in mannequin eyes. A rest impact was noticed inside the realm of the rings, more and more distinguished with the longer arc lengths and smaller optical zones.

“We did the identical with femto-CAIRS, and we couldn’t observe the identical stress distribution and rest within the inside a part of the corneal rings,” Torres-Netto mentioned. “We’d like extra research, however what we will say is that the rings made from human tissue have been very near the biomechanical habits of the affected person’s cornea. They don’t induce the unnatural stretching that PMMA rings induce.”

These outcomes result in two vital conclusions. First is that the nomograms which have been used thus far for artificial rings can’t be utilized to femto-CAIRS.

“The opposite conclusion is that the modifications that we see with femto-CAIRS are in all probability extra associated to the addition of quantity that the femto-CAIRS present reasonably than the biomechanical or stress distribution modifications,” Torres-Netto mentioned.

KeraNatural CAIRS

Aylin Kiliç, MD, was a pioneer in the usage of PMMA rings. They have been a part of her commonplace toolbox, and she or he appreciated the advantages they dropped at sufferers with keratoconus who didn’t have many choices. However she additionally noticed their limitations.

“The inflexible nature of PMMA rings merely didn’t match the unpredictable, dwelling habits of the keratoconic cornea,” she mentioned. “They lack predictability and carry the danger of stromal melting, extrusion and migration. I keep in mind pondering that there have to be a greater approach. One thing extra pure. One thing that works with the cornea, not in opposition to it.”

Aylin Kiliç, MD

Aylin Kiliç

The publication of Jacob’s first outcomes with CAIRS was a turning level. On the time, Kiliç was working with VisionGift and Allotex, exploring the usage of allogenic corneal tissue for a number of purposes.

“That’s when the thought got here: What if we might take the idea of intracorneal ring segments in a bundle?” she mentioned.

Along with VisionGift, Kiliç developed KeraNatural corneal allogenic intrastromal ring segments — packaged, standardized, designed particularly for keratoconus and with a 2-year shelf life.

“They’re prepared to make use of. There’s no must deal with or put together something within the working room,” she mentioned. “This not solely saves time but in addition dramatically improves sterility and reproducibility. It makes the process extra streamlined and extra accessible for surgeons in several settings.”

Over time, Kiliç and her workforce developed the Istanbul nomogram, a topography-guided system that permits for personalised remedy whereas sustaining some important requirements for consistency.

“We all the time use a femtosecond laser to create a standardized stromal tunnel, 4 mm to 7.5 mm in diameter at a depth of 250 µm. This provides us a secure basis,” she mentioned. “However the place the actual customization occurs is within the alternative of the allograft section. Its thickness, arc size and positioning are all adjusted based mostly on the person affected person’s corneal habits and topographic sample. That’s what makes the nomogram so efficient — it blends construction with flexibility.”

The big, superficial channels make it simple to insert the comfortable tissue of CAIRS and take away them if needed with out the necessity for drying or cross-linking to create stiffer inserts.

“We modified from PMMA to tissue. Why ought to we now insert tissue that’s as inflexible as plastic and stretch the cornea?” Kiliç mentioned. “I wish to make surgical procedure extra reversible, extra adjustable, and I don’t wish to stretch the cornea. That is my fundamental level. All methods are working very nicely, however long-term administration is essential.”

CTAK femtosecond laser-cut segments

OSN Cornea/Exterior Illness Board Member David R. Hardten, MD, FACS, was additionally not absolutely glad with PMMA rings, primarily as a result of they challenged the becoming of contact lenses. When Jacob described CAIRS, he began utilizing them.

David Hardten, MD

David R. Hardten

“In our follow, we name the process anterior lamellar keratoplasty with regional segments (ALKRS), primarily for insurance coverage causes, however it’s basically the identical as CAIRS,” he mentioned. “It was a giant evolution from PMMA rings. Contact lens becoming was now not an issue, and the tissue may very well be personalized, thicker or thinner, or broader, longer or shorter.”

Chopping, trimming and inserting the comfortable eye financial institution tissue by hand was, nevertheless, just a little difficult. When CorneaGen began producing CTAK femtosecond laser-cut segments, personalized on the Oculus Pentacam information of particular person sufferers, Hardten welcomed this novel alternative and began treating much more sufferers. CTAK, quick for corneal tissue addition keratoplasty, is commonly utilized in the US instead approach of naming CAIRS in one of many many iterations aimed toward making the process simpler and extra accessible.

“I consider CTAK as an evolution of that expertise, as a model title, so it’s like saying Kleenex vs. facial tissues,” Hardten mentioned. “We don’t truly name it CTAK in our follow. We proceed calling it ALKRS as a result of there’s not an insurance coverage code for CTAK or CAIRS. And you’re including tissue to the anterior cornea, so it truly is an anterior keratoplasty, and it’s lamellar as a result of it goes within the lamellar aircraft.”

The primary information on CTAK have been revealed by the group of Steven Greenstein and Peter Hersh, and Hardten’s group was one of many first to gather new information, not too long ago introduced on the American Society of Cataract and Refractive Surgical procedure assembly, on each keratoconus and post-LASIK ectasia.

“CTAK segments are the corneal allogenic tissue segments that the majority of us use within the U.S., partly as a result of they’re lower with the femtosecond laser, so the thickness and size are very correct,” Hardten mentioned.

He praised the “wonderful instinct” of Jacob in her surgical procedure; her potential to dimension the segments in line with corneal form, “some sections barely wider, some barely narrower, thinner or thicker to get the most effective outcomes”; and her confidence in transferring them to totally different areas, twisting them 20°, pulling them extra central, extra peripheral and even doing enhancements.

“We don’t have the identical expertise,” he mentioned. “Most of our sufferers are actually trying to get some enchancment, cease their development and have the ability to get again into contact lenses. Proper now, I’m comfortable to have one thing that may obtain these targets, and we don’t wish to create expectations we might not have the ability to meet.”

A versatile process

CAIRS surgical procedure, in all its deviations, is straightforward, quick, adjustable, augmentable and reversible, and it may be mixed with different procedures.

“When you don’t obtain the outcomes you anticipated, you may take away the segments, you may regulate them, and you’ll enlarge the channel and insert extra tissue,” Jacob mentioned.

She virtually all the time combines CAIRS with corneal cross-linking, which she performs simply after the insertion.

“I consider it corporations up the cornea in the absolute best form,” she mentioned. “Visible rehabilitation is quicker, and it additionally avoids these usually bilaterally affected sufferers from taking break day from work a number of instances.”

“CAIRS can also be a really adjustable process,” Jacob mentioned. “If for any cause the affected person progresses — due to rubbing the eyes, for example, or due to not cross-linking the affected person’s cornea — I could put in just a little little bit of extra tissue to get it again to the unique quantity of flattening after which do cross-linking once more. When achieved with the best approach, the speed of intraoperative issues is near zero, and the speed of postoperative issues can also be very low.”

CAIRS could be mixed with IOLs and phakic IOLs, with wavefront-guided or topography-guided PRK.

“I don’t mix it with laser as a result of I don’t like a subtractive process in keratoconus, however there are people who find themselves doing it,” Jacob mentioned. “My level is that it’s very suitable with all different surgical procedures”

Combining CAIRS with different keratoconus remedies, particularly cross-linking, is one thing Kiliç considers fastidiously, all the time aiming to tailor the method to every affected person’s illness stage and biomechanical profile.

“In some sufferers, I carry out CAIRS first, adopted by CXL in a staged method to stabilize the biomechanical modifications achieved with the ring,” she mentioned. “In others who’ve already had CXL, we carry out CAIRS secondarily to additional enhance their corneal form and imaginative and prescient.”

In a research, Kiliç analyzed 67 eyes with or with out prior cross-linking and located that the group with out prior cross-linking achieved better enchancment in imaginative and prescient and a stronger flattening impact on keratometric values.

“This implies that whereas CXL stabilizes the cornea, it could additionally make it extra proof against reshaping. So, the biomechanical stiffness from prior CXL could dampen the transforming response we regularly see with CAIRS alone,” she mentioned.

Hafezi and Torres-Netto have additionally been combining ECO-CAIRS with phototherapeutic keratectomy-assisted personalized epi-on corneal cross-linking (ELZA-PACE-CXL), wherein personalized map-driven PTK is carried out over the cone to take away the epithelium solely in that area. Epi-on cross-linking is then carried out on the cornea, with an epi-off window simply over the cone.

The timing of cross-linking in relation to CAIRS is determined on a person foundation.

“It relies on the affected person’s visible acuity, on whether or not keratoconus is progressing or not, and on whether or not the affected person has already had CXL earlier than and when. All these components play a job,” Torres-Netto mentioned.

Hardten performs cross-linking concurrently he does ALKRS in all his sufferers.

“We don’t need these sufferers to proceed to progress over time,” he mentioned. “ALKRS improves the form, and cross-linking retains them from persevering with to progress. And most of them have enchancment in greatest corrected imaginative and prescient with glasses. Most of them have enchancment in uncorrected imaginative and prescient. They will nonetheless put on a contact lens.”

In follow, CAIRS can be utilized flexibly as a stand-alone refractive and reshaping remedy, notably in clear, comfortable, non-cross-linked corneas, or together with cross-linking, both concurrently or sequentially, when long-term stabilization is the precedence, Kiliç mentioned.

“Finally, the choice is individualized. However what’s clear is that CAIRS stays efficient in each contexts, providing a protected and adaptive device in our keratoconus armamentarium,” Kiliç mentioned.

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For extra info:

Shady Awwad, MD, of American College of Beirut Medical Heart, Lebanon, could be reached at sawwad@gmail.com.

Farhad Hafezi, MD, PhD, of ELZA Eye Institute, Switzerland, could be reached at farhad@hafezi.ch.

David R. Hardten, MD, FACS, of Minnesota Eye Consultants, could be reached at drhardten@mneye.com.

Soosan Jacob, MS, FRCS, DNB, of Dr. Agarwal Eye Hospital, Chennai, India could be reached at dr_soosanj@hotmail.com.

Aylin Kiliç, MD, of Swiss Imaginative and prescient Group, Saryer/Istanbul, Turkey, could be reached at aylinkilicdr@gmail.com.

Emilio Torres-Netto, MD, PhD, of ELZA Eye Institute, Switzerland, could be reached at etorres@elza-institute.com.