Cornea
September 2023

by Liz Hillman
Editorial Co-Director

Editors’ note: This article was updated in June 2025 to include a few clarifications and additional historical context. 

Intracorneal ring segments (ICRS) were first introduced in the 1940s as a concept to treat myopia.¹ Fast forward to 2000 when they were proposed as a method to reduce corneal steepening in eyes with keratoconus.² In the 20+ years since, there have been several advances in the realm of intracorneal ring segments, both in terms of techniques and materials.

EyeWorld spoke with Philip Dockery, MD, MPH, Soosan Jacob, MD, and Aylin Kiliç, MD, to discuss the latest in the world of intracorneal ring segments.

“Intracorneal ring segments were first introduced as a way to treat low myopia before laser refractive surgery,” Dr. Dockery said of their history. “But when the excimer laser was introduced in the mid-90s with PRK and LASIK, which were much more accurate ways to reduce myopia and regular astigmatism, intracorneal ring segments fell out of favor in that population. However, later around 2000, they started to become in favor for the treatment of keratoconus, particularly mild, where the goal was to flatten the cornea and hopefully improve visual acuity. Intracorneal ring segments don’t halt progression of disease, but the goal is to improve vision about 2 lines on the Snellen chart.”

Synthetic ring segments

Synthetic segments and rings, such as INTACS (CorneaGen), Ferrara (AJL Ophthalmic), MyoRing (Dioptex), and KeraRing (Mediphacos),* are generally used in conjunction with crosslinking, which addresses progressive keratoconus, as a sequential procedure for improved visual acuity, whether that be with glasses, rigid gas permeable contact lenses, or uncorrected, Dr. Dockery said. Some of these, however, are described by the company as a treatment for progressive keratoconus.

From a safety standpoint, Dr. Dockery said that synthetic intracorneal inlays are relatively safe, but literature documents some concerning safety issues, such as segment extrusion, secondary bacterial keratitis, neovascularization around the segments, and segment migration. Dr. Dockery was the co-author on a study that looked at intracorneal ring segments in eyes with advanced vs. mild keratoconus, finding that visual and topographic effects were greater in eyes with more advanced keratoconus, and there was no increased incidence of common complications in this patient population.³

One of the challenges with synthetic segments and rings, Dr. Jacob said, is the limitation with smaller optic zones.

“ICRS were initially implanted at a larger optic zone, but soon it was understood that to get a better effect, there was a requirement to use smaller optic zones, so the optic zone in the case of INTACS shrunk from 6.8 to 6 mm. The KeraRing is available at a 5 mm optic zone. None of the synthetic ICRS go below this for obvious reasons. One is as we go centrally, the cornea becomes thinner, and we know that synthetic ICRS can lead to extrusions, melts, intrusions, etc., and this is more common if there is not sufficient corneal tissue to cover the ICRS,” Dr. Jacob explained. “In addition, even though greater effect may be obtained by implanting in even smaller optic zones, the probability of corneal melt as well as halos and glare are high enough that in optic zones smaller than 5 mm these are not used at all.”

Dr. Jacob said advancements in intracorneal ring segments include a decrease in diameter shape, a triangular shape (which helps go to the 5 mm optic zone, deflecting light away from the visual axis and preventing halos), different arc lengths (ranging from 90–120 degrees), and more asymmetric shapes with varying thicknesses.

Allogenic ring segments

The use of allogenic tissue was first introduced by Dr. Jacob in 2015 as CAIRS (corneal allogenic intrastromal ring segments), and it refers to intracorneal placement of fresh, unprocessed, processed, preserved, or packaged allogenic rings or segments of any type or length.⁴ In the paper, Jacob et al. described using a double-bladed trephine on a donor cornea and implanting the tissue obtained into femtosecond laser-dissected corneal channels. This was followed by accelerated crosslinking. This pilot study included 24 patients with keratoconus, stage 1 to 4, with 6–18 months of follow-up. The procedure resulted in significant improvement in UDVA, CDVA, and other improvements.

Since then, Dr. Jacob has enhanced the CAIRS procedure with customization. She said it can be implanted in small optic zones (4.2–4.3 mm), and arc length, thickness, and shape can be customized for individual patient needs.

“This customization can be done to match exactly to the patient’s topography, unlike the synthetic segments where fixed thickness or width gradations are present (i.e., there is a fixed gradient from one end to the other),” she said. “In CAIRS … the gradient can change extremely locally as per the patient’s topography. This can be done using the Jacob CAIRS Customizer [Epsilon Instruments] and the manual Jacob CAIRS Trephine [Madhu Instruments] or using the femtosecond laser.”

Dr. Jacob said CAIRS can be implanted more superficially than synthetic segments, allowing a greater effect without the risk of corneal melts.

Dr. Jacob said more than 600 patients with all grades of keratoconus have undergone CAIRS. “The patient experience has been very positive with patients reporting a decrease in distortion and improvement in visual acuity,” she said. “The refractive error comes down and becomes more tolerable. Most have bilateral disease and undergo sequential bilateral surgery, again showing that they like the outcome from the surgery. In addition, many refer their friends from support groups or other known contacts who suffer from ectasia. CAIRS has also been accepted with enthusiasm by keratoconus specialists around the world, indicating its safety and efficacy.”

Dr. Jacob said that compared to DALK, CAIRS is minimally invasive with less of a learning curve. Compared to other allogenic technologies, such as lenticule implantation, CAIRS leaves the visual axis untouched. Compared to subtractive techniques, such as topography- guided PRK, Dr. Jacob said there is no risk of destabilizing non-progressive keratoconus with CAIRS.

“Being an additive technology, [CAIRS] has the advantage of being able to harness a much greater amount of effect. In subtractive techniques, the effect that can be obtained has to be balanced against the risk of inducing progression of keratoconus because of the amount of tissue removed. Thus, large effects cannot be obtained,” she said.

Dr. Dockery thinks one of the biggest advantages of allogenic segments over synthetic is improved safety, while having a greater impact of improving corneal shape. He also said CAIRS can be used in more advanced cases. “We’ve implanted some of these segments in eyes with a Kmax in the 90s even,” he said. He added that he has seen more flattening with CAIRS than with synthetic segments.

“Some eyes will see even 20–30 D of flattening, which is much more. However, what we’ve realized is that the level of flattening is not always predictive of the level of visual acuity improvement or the quality of improvement of vision,” he said. “The thing we’re looking at now is we’re seeing a significant decrease in higher order aberrations after CAIRS implantation … making the quality of vision better and making these corneas possibly more refractable.”

Dr. Kiliç was involved in the development of KeraNatural (VisionGift), which she described as an allogenic corneal inlay that is obtained from VisionGift eye banks and packaged in a process that is shelf stable for 2 years. “It is amazing. … It is packaged like a contact lens,” she said.

Dr. Kiliç described the Istanbul protocol, which includes implanting the KeraNatural tissue into femtosecond laser-created tunnels, followed by crosslinking if keratoconus is progressive. She said that segment length can be customized based on the topographic regularization that’s needed, and more than one segment can be used as well. This protocol that was published was a pilot study in 2022, showing an increase of CDVA from a mean of 0.29±0.20 preop to 0.56±0.26 post-KeraNatural.⁵

A more recent retrospective, non-randomized study of 65 keratoconic eyes of 49 consecutive patients (mean age 29.5±7.3 years) found KeraNatural helped improve UCVA from 0.91±0.50 logMAR preop to 0.40±0.24 logMAR at 6-months postop; CDVA improved from 0.87±0.20 logMAR preop to 0.27±0.06 logMAR postop.⁶ Average keratometry decreased from 49.23±5.22 to 45.63±4.89 D with KeraNatural. The investigators reported that mean anterior and posterior maximum elevations significantly decreased as well.

“This study demonstrated that implantation of corneal allograft ring segments is a viable alternative treatment for keratoconus with safety and good visual results,” Nacaroglu et al. wrote.

Dr. Kiliç said efficacy is similar to synthetic intracorneal ring segments but without the complications. “This is extremely safe biologic tissue,” she said. “We think it is safer than keratoplasty. It’s a 5- to 10-minute procedure. It’s reversible. It’s adjustable. I think all keratoconus patients should be given a chance with KeraNatural.

“My mission is to stop keratoplasty for keratoconus in the world. [The KeraNatural] allograft tissue is from one cornea and we can obtain so many; so many keratoconus patients can benefit,” Dr. Kiliç said later.

*This list may not be comprehensive of all synthetic intracorneal ring segment products.

Update: June 2025

Thomas Loarie, former chairman and CEO of KeraVision, reached out to EyeWorld to offer additional historical context on the early development of INTACS, which were pioneered by KeraVision. Mr. Loarie led KeraVision from 1987 until its acquisition in 2002 by Addition Technologies.

Mr. Loarie wrote in an email to EyeWorld that in an FDA clinical trial, INTACS delivered more accurate myopia and regular astigmatism correction than PRK and LASIK in the 1990s. He noted that despite the trial showing efficacy for up to –5 D of correction, the FDA limited the indication for INTACS to correct –3 D. “This restriction hampered our ability to serve the patient population most likely to seek surgical correction. The larger ring sizes were eventually approved after further studies that closely mirrored our original data,” Mr. Loarie said.

In addition to this regulatory limitation, Mr. Loarie said economic barriers played a role in slowing INTACS adoption. “By the late 1990s, most refractive surgeons had made substantial investments—often nearing $1 million—in LASIK infrastructure and marketing. Many were understandably hesitant to adopt a competing approach, no matter how compelling the data,” he said.

INTACS, in addition to use for keratoconus, were used to treat post-LASIK ectasia, pioneered by Michael Kritzinger, MD. “His clinical innovation helped reshape how INTACS were viewed beyond refractive correction,” Mr. Loarie said.

“KeraVision also contributed several technical advancements to the field, including the early use of finite element modeling to iterate design and predict optical outcomes—a system spearheaded by Thomas Silvistrini, Vice President of R&D, in collaboration with Stanford University. This approach was quite novel in ophthalmology at the time and formed a core part of our product development,” Mr. Loarie said.

In addition, Mr. Loarie mentioned the work of Gene Reynolds, OD, and his development of the CorneaScope for producing topographical images of the cornea, which he said played a pivotal role in the initial concept of INTACS. “It was through his work, and advice from Dr. David Schanzlin, that the concept evolved from central expansion to the peripheral-thickening approach inspired by Ignacio Barraquer, MD,” Mr. Loarie said. “While KeraVision may not have become a household name, the work of our team—Gene Reynolds, David Schanzlin, Michael Kritzinger, Joseph Colin, and others—made lasting contributions to both refractive and therapeutic corneal surgery.”

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About the physicians

Philip Dockery, MD, MPH
Harvey and Bernice Jones
Eye Institute
University of Arkansas for Medical Sciences
Little Rock, Arkansas

Soosan Jacob, MD
Director
Dr. Agarwals Refractive & Cornea Foundation
Dr. Agarwals Eye Hospital
Chennai, India

Aylin Kiliç, MD
Medical Director and Founder
Swiss Vision Group
Istanbul, Turkey

References

1. Barraquer J. Modification of refraction by means of intracorneal inclusions. Int Ophthalmol Clin. 1966;6:53–78.
2. Colin J, et al. Correcting keratoconus with intracorneal rings. J Cataract Refract Surg. 2000;26:1117–1122.
3. Dockery PW, et al. Intracorneal ring segment implantation in advanced keratoconus. Eur J Ophthalmol. 2023;33:1324–1330.
4. Jacob S, et al. Corneal allogenic intrastromal ring segments (CAIRS) combined with corneal cross-linking for keratoconus. J Refract Surg. 2018;34:296–303.
5. Haciagaoglu et al. Allograft corneal ring segment for keratoconus management: Istanbul nomogram clinical results. Eur J Ophthalmol. 2022. Online ahead of print.
6. Nacaroglu SA, et al. Efficacy and safety of intracorneal allogenic ring segment implantation in keratoconus: 1-year results. Eye (Lond). 2023. Online ahead of print.

Relevant disclosures

Dockery: None
Jacob: Patent granted for special trephines and devices used to create these segments, patent pending for CAIRS segments and various types of shaped corneal segments, Madhu Instruments, Ziemer Ophthalmic Systems
Kiliç: VisionGift

Contact

Dockery: phildock2020@gmail.com
Jacob: dr_soosanj@hotmail.com
Kiliç: aylinkilicdr@gmail.com