Future of IOLs: Modular, shape-changing, multifunctional
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Replicating the physiological mechanism of focusing of the crystalline lens with an IOL has been the long-time ultimate goal of presbyopia management.
Several attempts seemed successful at first but eventually failed because fibrosis occurred with time, reducing the ability of the capsule to contract and move the lens. The search continues, and new projects are in the pipeline, with novel designs and mechanisms of action.
Source: Erin Shin, RN
“We have learned many lessons over the years on the challenges associated with utilizing the accommodative mechanisms of the natural eye, which turned out to be far more complex than we had ever anticipated,” Healio | OSN Presbyopia Section Editor George O. Waring IV, MD FACS, said. “The pilot data and the early clinical data that are emerging from the numerous contemporary shape-changing designs appear very promising, and there is consequently a renewed interest and optimism in this space. Here is the opportunity to further increase the range of focus while minimizing or hopefully eliminating dysphotopsia.”
Modular systems that allow for stable placement and easy replacement of IOLs are another new frontier.
“The old paradigm of cataract surgery as a one-time intervention is changing. As physicians, we need to start embracing the idea that our patients are going to want to have access to better technology as it arrives,” Healio | OSN Technology Board Member Gary Wörtz, MD, said.
These emerging technologies overlap in concept in some of the new upcoming IOLs, which are both shape-changing and modular.
“We can give patients flexible focusing without the compromise of diffractive optics. And also, with the promise of modularity, we give them the ability to upgrade in the future,” Healio | OSN Cataract Surgery Board Member Sumit “Sam” Garg, MD, said.
OmniVu
At this year’s American Society of Cataract and Refractive Surgery meeting in San Diego, Waring presented the first-in-human results for the OmniVu IOL system (Atia Vision).
This IOL is a modular shape-changing system with a fixed-power front optic and a fluid-filled shape-changing base that is responsive to the movements of the ciliary muscle. Following a 5.5-mm manual capsulotomy, the fluid-filled base lens is inserted in the capsular bag, and once positioned, the fixed-power front optic lens is docked into the base.
“The natural accommodative mechanism of the eye, when stimulated, activates the fluid-filled base, changing its shape and increasing the range of focus,” Waring said.
At the meeting, he shared the data on 25 eyes of 18 patients, which look promising in both safety and efficacy. Monocular uncorrected vision was 20/20 at distance, 20/25 at intermediate and 20/32 at near 6 months postop, with good stability. In terms of predictability, 95% of patients were within 0.5 D of the intended target, which was plano at 6 months. After binocular implantation, uncorrected vision averaged 20/16 at distance, 20/20 at intermediate and 20/32 at near, suggesting a broad range of vision with a continuous defocus across more than 4 D. Visual symptoms, quality and contrast sensitivity were comparable to those of monofocal IOLs.
“We are currently working on the investigational device exemption to start the U.S. FDA clinical trials,” Waring said.
Juvene
The Juvene IOL (LensGen) is another modular shape-changing system. A bag-filling base haptic surrounding a fixed-power lens is implanted in the capsular bag, and a shape-changing fluid lens is then inserted and tabbed into place within the haptics.
“The two parts are injected separately, the base lens first followed by the fluid lens, through a 3- to 3.2-mm incision,” Garg said. “We believe it is the anterior shape-changing aspect of the IOL that allows for continuous vision from distance to intermediate to near upon accommodative stimuli.”
Garg has personally implanted several of these lenses and reported at the ASCRS meeting the 3-year data of the Grail exploratory study performed at two sites in Mexico. Monocularly, mean distance vision was 20/18, intermediate was 20/25 and near was 20/35, further improving with binocular summation.
“What we’ve shown is maintenance of the accommodative amplitude up to 3 years. The range of vision was very good, and we didn’t lose any effect over time. There was no PCO, endothelial cell loss was similar to that of standard cataract surgery, and patient satisfaction was high,” he said.
With multifocal lenses, range and quality of vision are to some extent conflicting and inversely correlated, while with lenses such as the Juvene, it is possible to have range and quality at the same time, Garg said.
“With this lens, you get the range, as you would expect, but at the same time, you also get really excellent patient satisfaction and minimal, if any, dysphotopsia,” he said.
Using an advanced computerized system (Clinical Trial Suite, M&S Technologies), contrast sensitivity of the Juvene was similar to that of a high-quality monofocal lens, namely the Tecnis monofocal (Johnson & Johnson Vision).
“The lens produces a 2 D to 3.5 D increase in power, and that is distance corrected, so it is not monovision. Whenever you look at data, you have to make sure that it is not a myopic offset, or using one eye vs. the other,” Garg said.
The next step will be a phase 1 clinical trial in the U.S. The COVID-19 pandemic slowed down research in many non-COVID-related fields, but now the company is in the process of raising funds to move forward.
“There is also a toric version that is underway, and the modular system offers the added benefit of potentially exchanging or upgrading the optic at any time in the future. I am really quite excited about the possibilities of this lens for our patients,” Garg said.
JelliSee
The JelliSee IOL (JelliSee Ophthalmics) is a silicone lens that mimics a child’s lens in form and function, Healio | OSN Presbyopia Board Member John A. Vukich, MD, said.
It is made of a stable posterior element that has a base refractive power and a dynamic anterior portion that responds to the movements of the capsule. Eight equally spaced actuators are attached circumferentially around the anterior surface of the lens.
“Actuators” is what haptics are called in this lens because they have a specific function, which is to couple the movement of the capsule to the anterior surface of the lens, creating a shape change. Vukich explained that the majority of the translated mechanical force in a natural human lens results in reshaping the anterior surface, and this is what happens with the JelliSee IOL.
“The lens is designed to mimic the lens of a child, meaning that the posterior surface has more of the dioptric power and the anterior surface is relatively flat, like a human lens in the disaccommodation state. A given amount of change in radius or movement in a relatively flat surface has a higher dioptric power change than the equivalent change in an already curved surface, and this is the fundamental idea of the lens,” Vukich said.
In other words, the focus shifts from very near to very far with just a fraction of millimeter in diameter change of the anterior surface of the lens. More than 6 D of accommodation requires less than 0.2 mm of diameter change.
In an eye that has undergone cataract surgery, the lens capsule will fibrose and contract over time. While this natural process has led to the failure of many accommodating IOLs, the JelliSee lens uses it to its advantage.
“The coupling of the actuators to the fibrotic lens capsule, and consequently to the zonules, is actually potentiated by capsular contraction, which increases the amount of translated energy from the ciliary body to the lens,” Vukich said.
Implantation is straightforward through a standard injector, which is currently 3.2 mm but could potentially be smaller. The eight points of fixation provide good stability, ideal for a future toric model.
The results so far have been encouraging.
“The amplitude of accommodation is so great that we are now aiming for +1 D as our refraction. We are routinely getting 7 D defocus curves, and in our data set, we are measuring near and ultra-near, at 15 cm to 20 cm, and patients are able to see J1-plus,” he said.
The in-human proof-of-concept study with 10 patients implanted in El Salvador is now complete, and a new study will start in the third quarter.
FluidVision
The FluidVision IOL (Alcon) is a hollow acrylic lens filled both in the optic and haptics with silicone fluid. During accommodation, the fluid is squeezed from the haptics into the optic, which changes shape and power. In the disaccommodation state, the fluid moves in the opposite direction.
Several single-center and multicenter studies have been performed, showing that the visual acuity gains at all distances were maintained up to 4 years of follow-up. The ORION multicenter study comparing the FluidVision with the monofocal AcrySof IQ (Alcon) showed that the lens is capable of up to 2.2 D of accommodation, providing good intermediate and near vision. Contrast sensitivity was comparable to that obtained with the comparator. In addition, the CLEAR multicenter study is underway, comparing the FluidVision to trifocal IOLs.
“The lens has been in development for a long time, and the new iteration has recently been presented at the ASCRS meeting,” Garg said. “The company is also working on a tunable technology, which will allow the surgeon to tune the lens post-implantation to achieve optimal distance vision.”
Incision size should also be decreased from the current 3.5 mm to 2.8 mm.
Lumina
The Lumina IOL (Akkolens) consists of two optical elements that slide horizontally across one another in a plane perpendicular to the optic axis, inducing changes in focal power. The lens is implanted in the sulcus, overcoming the issues related to postoperative capsular bag fibrosis and contraction.
“It is a varifocal lens system. During accommodation, when the ciliary muscle contracts, the sulcus-to-sulcus distance decreases and the two optical elements change position, leading to an increase in dioptric power and focusing of light for the near distance,” Jorge L. Alió, MD, PhD, said.
The first Lumina lenses were implanted 15 years ago. Studies up to phase 3 were performed in Bulgaria and Spain, and more than 10 years of follow-up data give evidence that the lens works in the long term.
“We have achieved spectacle independence in 90% of the patients, and 10% use a small near vision add. Distance vision is excellent, intermediate is perfect, and near vision is at the level of J2 to J3 in 95% of the cases. The lens is also pupil independent and doesn’t induce any type of halos, glare or distortion,” Alió said.
The Akkolens has already obtained the CE mark and is expected to be commercialized in Europe next year.
Harmoni
The main advantage of modular or multicomponent IOLs is the possibility to exchange them without incurring the complication of classic IOL removal.
“The nice thing about a lens such as the Harmoni modular IOL (Alcon) is that there’s a base unit that completely fills the lens capsular bag, and then the optic is secondarily attached to the base unit. So, if you need to exchange the lens, you don’t disturb the capsular bag because the base unit is still in place. You remove the optic unit and put a new optic unit into the eye,” Nick Mamalis, MD, said.
Both units are implanted separately through a standard small incision with a standard injector cartridge.
A further advantage is that the base unit, by filling up the capsular bag, effectively prevents posterior capsule opacification (PCO). This was shown by the extensive studies conducted by Mamalis and his group on a rabbit model.
“One of the advantages of a rabbit model is that proliferation of lens cortical material occurs very rapidly after cataract surgery. So, we can simulate in 4 to 6 weeks the amount of PCO that will develop in humans in 2 to 3 years. By implanting the Harmoni lens in one eye and a standard lens in the other eye, we found that 6 to 8 weeks later the capsular bag with the Harmoni lens was quite clear, whereas with the standard hydrophobic acrylic lens, there was a large amount of proliferative cortical material and PCO,” he said.
This translates in clinical practice into less need to perform YAG capsulotomy, he said.
The Harmoni IOL is currently available with a standard monofocal optic. It received the CE mark in 2015.
fixOflex
The fixOflex ring (Eye PCR) has a stable internal structure to hold the IOL optic and a flexible periphery to adapt to different capsule sizes.
“The idea behind it is to preserve the shape and volume of the capsule. The optical part of an IOL is placed in a very steady environment, with no surprises in the long term, and all problems of predicting the effective lens position for IOL power calculation are overcome because you know exactly at which level the IOL is located. In addition, PCO and any fibrosis effect are eliminated. Also, peripheral dysphotopsia is blocked, and vitreous body is stabilized,” Ioannis Pallikaris, MD, PhD, said.
Interchangeability is another advantage, critical today with the increasing adoption of multifocal IOLs and the higher number of post-LASIK and post-PRK corneas.
“Exchange might be required in the future for many reasons because patients may want to change their IOLs with upgraded technologies or with a telescopic lens if they develop age-related macular degeneration. And there is great scope for the fixOflex ring in pediatric surgery for easy IOL exchange as the eye develops and for preventing PCO, which is aggressive in children,” Pallikaris said.
More than 250 fixOflex rings have been implanted so far, with official trials at Alexandria University, Egypt, and the University of Heraklion, Crete, Greece.
“We have used the ring with the J&J IOLs and the Alcon PanOptix in the studies, but we have used also other types of C-loop IOLs, including the IC-8 Apthera (Bausch + Lomb),” Pallikaris said.
Gemini Refractive Capsule
The Gemini Refractive Capsule (Omega Ophthalmics) is a modular and potentially multifunctional system that acts as a scaffold for IOLs and also serves as a platform for drug delivery and biometric-sensing technologies.
“It is a three-dimensional capsular ring that can be paired with all single-piece C-haptic IOL designs and three-piece IOL designs and holds them stable inside the capsule, also preventing fibrosis. We have tested the Alcon and J&J IOL platforms with good success,” Wörtz said.
Because the crystalline lens is more voluminous than an IOL, additional space has been allowed within the Gemini capsule, which can be used, for example, for drug delivery implants or IOP sensors.
“Essentially, we have created a receptacle for technology to both exist and be exchanged or upgraded throughout the patient’s lifetime for both improved vision and disease state monitoring and treating,” Wörtz said. “Since about 30% of patients with glaucoma don’t take their drops adequately, here we have the space to treat multiple years of glaucoma with a sustained-release implant that’s inside the capsule, away from the cornea and from the endothelium, and when the drug dissolves, the space becomes available for reimplantation.”
The Gemini is easy to implant with a standard injector and self-expands in the capsular bag. A study performed in Costa Rica on 30 patients with 1 year of follow-up showed good safety, and an ISO certification process is in preparation for a European trial.
Looking forward
The future of intraocular implants may lie in these multifunctional modular systems in which the optical component is just one part, and another technology component could be added to monitor ocular or systemic parameters, deliver therapies or incorporate virtual reality systems.
“The exciting feature of modularity is that it opens up all kinds of possibilities for biosensing, drug delivery or things that we may not even know about right now because it keeps the capsular bag open,” Garg said.
“Anything that you do on a computer now has just been put into a pair of goggles by Apple. In the future, we predict we will be able to take that exact same technology and put it into an intraocular lens,” Waring said.
Interchangeability will be key to meet patients’ needs and anticipate how they are going to change over a lifetime.
“We will be able to provide a platform solution that allows patients to really be in charge of how they want to see and take advantage of technology as it evolves,” Wörtz said.
- References:
- Alio JL, et al. Surv Ophthalmol. 2017;doi:10.1016/j.survophthal.2017.03.005.
- Ang RET, et al. J Cataract Refract Surg. 2021;doi:10.1097/j.jcrs.0000000000000654.
- Bontu S, et al. J Cataract Refract Surg. 2021;doi:10.1097/j.jcrs.0000000000000391.
- Chang DH, et al. Clin Ophthalmol. 2021;doi:10.2147/OPTH.S318065.
- Garg S, et al. J Cataract Refract Surg. 2022;doi:10.1097/j.jcrs.0000000000000935.
- Garg S, et al. Thirty-six-month visual outcomes after implantation of a modular, shape-changing, fluid-optic intraocular lens. Presented at: American Society of Cataract and Refractive Surgery meeting; May 5-8, 2023; San Diego.
- Guan JJ, et al. Clin Exp Ophthalmol. 2016;doi:10.1111/ceo.12786.
- Kennedy S, et al. J Cataract Refract Surg. 2021;doi:10.1097/j.jcrs.0000000000000367.
- Ludlow J, et al. Acta Ophthalmol. 2018;doi:10.1111/aos.13674.
- MacLean KD, et al. Clin Exp Ophthalmol. 2015;doi:10.1111/ceo.12526.
- Pepose JS, et al. Asia Pac J Ophthalmol (Phila). 2017;doi:10.22608/APO.2017198.
- Pepose JS, et al. Curr Opin Ophthalmol. 2017;doi:10.1097/ICU.0000000000000323.
- Waring GO, et al. Prospective, open-label, non-randomized, trial of a presbyopia-correcting, modular intraocular lens system for treatment of cataract. Presented at: American Society of Cataract and Refractive Surgery meeting; May 5-8, 2023; San Diego.
- For more information:
- Jorge L. Alió, MD, PhD, of Vissum Corporation, Alicante, Spain, can be reached at jlalio@vissum.com.
- Sumit “Sam” Garg, MD, of University of California, Irvine, can be reached at gargs@uci.edu.
- Nick Mamalis, MD, of John Moran Eye Center, University of Utah, can be reached at nick.mamalis@hsc.utah.edu.
- Ioannis Pallikaris, MD, PhD, of Vardinoyiannion Eye Institute of Crete, School of Medicine, University of Crete, Greece, can be reached at email: pallikar@gmail.com.
- John A. Vukich, MD, of Summit Eye Care, Wauwatosa, Wisconsin, can be reached at javukich@gmail.com.
- George O. Waring IV, MD, FACS, of Waring Vision Institute, Mt. Pleasant, South Carolina, can be reached at gwaring@waringvision.com.
- Gary Wörtz, MD, of Commonwealth Eye Surgery, Lexington, Kentucky, can be reached at 2020md@gmail.com.
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