New frontiers in IOL technology aim at flexible, customized solutions

Despite decades of trying to optimize results and despite the many advances in IOL technology, achieving optimal refractive outcomes and meeting patient expectations with cataract surgery are still challenges. Results are subject to many variables, and looking at statistics, only about half of patients are within the high satisfaction range of achieving 0.5 D of emmetropia and 0.5 D or less of astigmatism.

Pseudoaccommodative multifocality is the technology that has evolved the fastest. New models have improved visual quality, and patient satisfaction is generally good. However, multifocality has inherent optical compromises, resulting in photic phenomena and contrast sensitivity loss.

Source: Jay S. Pepose, MD, PhD

“Whenever we are splitting the light between multiple points, we have two or more images superimposed on the retina, and the out-of-focus image always creates some type of diffractive pattern. So, you have to explain to the patients that there is going to be a tradeoff, that they might experience glare, halos and spider web patterns. Fortunately, because the brain is a very good visual processor, most people eventually neuroadapt,” Jay S. Pepose, MD, PhD, said.

Research on optimal cataract surgery outcomes is also looking beyond multifocality in the quest for predictable, stable and accurate refractive outcomes, tailored to individual needs and responses.

Accommodating IOLs through multiple generations

“If there were a true accommodating lens that provided an effective and stable 3 D of accommodation, we would look back at multifocals, trifocals and EDOFs as a thing of the past,” Pepose said.

Compared with pseudoaccommodation, real accommodation is a more complex goal, toward which several attempts have failed or only modestly and temporarily succeeded. However, through these attempts a lot has been learned about the physiology of accommodation and the biological processes occurring in the capsule after cataract removal. Capsular bag contraction and fibrosis were shown to affect the mechanism of single-optic accommodating implants, and the concept of focus change by forward and backward displacement was questioned by ultrasound biomicroscopy and OCT studies. The axial movement of these lenses alone was not enough to account for even 1 D of accommodation, but depth of focus can be enhanced by other positional mechanisms such as lens tilt.

“There is a lot of interest in upcoming shape-changing intraocular lenses,” Pepose said. “We have seen tremendous progress with the FluidVision accommodating IOL (Alcon). It has come through multiple designs, and the fifth-generation FluidVision 20/20 is now undergoing clinical trials. The early results are highly positive, and there are plans for producing the lens in different sizes.”

The FluidVision exploits fluid dynamics within the lens in response to the forces within the capsule, which constricts and relaxes in the process of accommodation. Fluid is driven from the haptics to the optic and back, changing the curvature and consequently the power of the lens. The large haptics keep the anterior and posterior capsule apart, reducing capsular fibrosis.

“Previous studies with the fourth generation of the lens showed very good vision at all distances, 3 D of monocular and 4 D of binocular accommodation, and stability over 24 months,” Pepose said.

Incision size is currently a limitation. The IOL is implanted with an injector through a 3.5-mm incision, and the next question will be how small the incision can be to allow this type of lens in the eye, Pepose said.

A solution for smaller incisions

With the Juvene accommodating IOL (LensGen), the issue of size was addressed by splitting the lens in two different components that can be inserted through a smaller incision.

“It is a modular system made of a fixed lens and a fluid-filled flexible lens that provides reading vision. The first fills the entire volume of the capsule and acts as a scaffold for the fluid-filled lens. In response to the capsular movements during accommodation, the anterior optic of the fluid-filled lens undergoes shape changes that translate into near vision,” OSN Cataract Surgery Board Member Sumit “Sam” Garg, MD, said.

This lens has undergone several iterations over the years. The latest design is currently being evaluated in the international GRAIL trial, and early results show reproducible 3 D of accommodation, best corrected visual acuity of 20/20 in 85% of eyes at distance, excellent intermediate vision and 20/32 at near in 50% of the eyes studied.

Some of the patients implanted with the previous model have now reached 4 years of follow-up.

“The two designs are quite different so it would be like comparing apples and oranges, but 4 years tells us something about safety. The silicone material is well-tolerated, and we have seen very little PCO, likely because the capsular bag is filled by the lens,” Garg said.

Garg had the opportunity to implant this lens recently and initially doubted the possibility of inserting it through a small incision.

“Looking at the lens, you think, ‘Well, that’s big. How am I going to make it fit?’ Then it becomes all quite natural. The base lens is injected through a standard 3-mm incision just like a regular IOL and unfolds very easily into the capsular bag. Then you insert the fluid-filled lens and secure it to the base lens with three tabs. I was expecting more of a learning curve, but the whole process is actually quite intuitive,” Garg said.

This lens holds the promise of regaining near vision without the drawback of dysphotopsia, which is experienced even with the newest trifocal and extended depth of focus lenses. Further benefits may include a low rate of posterior capsule opacification and less stress on the vitreous and retina.

“Because the lens is filling the bag and curvature changes occur without traction, there is less stress on the vitreous cavity, with potentially the extra safety benefit of less [posterior vitreous detachment] and less retinal tear,” Garg said.

IOLs that fill in the capsular bag are also more predictable and stable with respect to lens position.

“Long-term data and UBM studies have shown that the effective lens position of the Juvene lens is stable over 4 years, and in the GRAIL study, refractive targeting so far has been really excellent,” he said.

‘Open access’ platform

Effective lens position is a crucial factor in the refractive success of cataract surgery, a variable in biometry that currently remains one of the main sources of error.

“Effective lens position is a mythical concept of where the lens will sit after healing is accomplished. We implant a lens that is much thinner than the natural lens, and the position of this lens will depend on how the zonules contract and the capsule collapses around it,” OSN Technology Board Member Gary N. Wörtz, MD, said.

Frustrated by variable and unpredictable results after well-done surgery, Wörtz developed the concept of a framework inside the capsule in which the lens would sit in a stable position.

The Gemini refractive capsule (Omega Ophthalmics) is a silicone three-dimensional platform capsular tension ring with two openings that is implanted after cortex removal. It keeps the capsular bag open in a natural conformation while at the same time holding the lens.

“We are building a proprietary lens for this technology, but the true advantage is that it can be used with any kind of lens and also with other technologies such as telescopes, IOP sensors and long-term drug delivery mechanisms. And, whatever implant we insert is easily explanted through a small incision, less than 2.75 mm,” Wörtz said.

Lenses can be fixated on the top or bottom opening of the Gemini capsule, or on both in case of dual-optic systems. This provides the option for piggyback implantation and potentially for dual-optic accommodative systems. Exchanging IOLs may be simple because any implanted lens will be away from the natural capsule and therefore not affected and blocked by fibrosis.

“There will finally exist the option to adjust refraction by exchanging a lens or to upgrade to newer lenses as technology advances over time,” Wörtz said.

He defines the Gemini refractive capsule as an “open access” platform that not only reduces refractive variability but also gives maximum flexibility in terms of IOL choice, exchange, adjustability and integration with other technologies. Feasibility studies are currently ongoing in different locations worldwide, and some small design modifications for fine-tuning are underway.

Paradigm shift of adjustable optics

Adjustable optics that are shaped in the eye after implantation are another paradigm shift in cataract surgery. Born from an idea from Daniel Schwartz, MD, in the mid-1990s, the RxSight Light Adjustable Lens (LAL) was approved by the FDA in 2017.

OSN Refractive Surgery Board Member Vance M. Thompson, MD, was principal investigator for the U.S. FDA monitored clinical trials. He said that the LAL is a three-piece foldable silicone lens containing photoreactive macromers that polymerize when irradiated by UV light. To reestablish an equilibrium, the macromers from the non-irradiated area diffuse into the polymerized portion of the lens, causing a shape change.

“If you irradiate the central area, the other macromers will diffuse into that area, increasing corneal curvature, and if you irradiate the peripheral area, the macromers diffuse peripherally, decreasing the curvature,” Thompson said.

Based on this principle and using specific formulas, myopia, hyperopia and astigmatism can be treated on the lens in a fully customized fashion after healing has occurred. Precision monovision can also be planned to address presbyopia.

“Two to three weeks after surgery, we can simulate various refractive options and customize the power of the lens based on what patients want. If they are not satisfied, two further adjustments can be made before a ‘lock-in’ procedure stabilizes the lens power,” Thompson said.

This procedure not only leads to refractive accuracy but also takes a lot of pressure out of the decision-making process during preoperative cataract counseling.

“Currently, we spend a lot of time ‘painting pictures with words’ because you cannot show a patient with a cataract how he or she is going to see,” Thompson said. “With the LAL, postop is the new preop. Patients don’t have to make a decision with a cataract in their eyes. They can wait until postop and then choose the lens option that works best for their brain and their optical system, and they can live with it for a while before locking it in.”

Before the LAL is locked in, patients need to wear protective spectacles to prevent unwanted changes to the power of the lens resulting from UV light exposure. Thompson said that in his experience patients accept this small inconvenience well because they are highly motivated.

“For the first time in cataract surgery, they can get an implant that is totally customizable inside their eye, and this is a very powerful concept. Recruitment in the study was very easy because patients brought in other patients,” he said.

The LAL allows for postoperative refractive accuracy comparable to that of LASIK. In phase 3 studies, 92% of the patients were within 0.5 D of manifest refraction spherical equivalent. Uncorrected distance vision was up to 20/16 or 20/12 in many patients.

“Uncorrected distance vision is the main driver of patient satisfaction after cataract surgery, and with the LAL, there is no further enhancement you have to do. You achieve such an accurate treatment without having to deal with dry eye, tear film instability, operating on the cornea or long time delay. It is an exciting future for refractive cataract surgery with such an increased chance of visual success,” Thompson said.

Refractive index shaping

Jason Jones, MD, who was also involved in the clinical trials of the LAL, believes in even further advances of the postoperative adjustment technology.

“The LAL and other techniques to manipulate an IOL require a lens that is specific to the modifying process. The Perfect Lens refractive index shaping (RIS) process makes potentially every IOL adjustable,” he said.

Using a femtosecond laser and an optical focusing system, a 50-µm layer within the lens is treated to produce a preset refractive index modification. The procedure can be performed at any time after postoperative stability has been achieved.

“RIS gives you a lot of flexibility in terms of time, and on a conceptual basis more than one treatment can be performed because it only affects one layer. Potentially, you can also reverse the previous treatment — say you have done a plus power change, you can reverse it with a minus power change, as long as you use a different layer,” Jones said.

Likewise, Clerio Vision is developing femtosecond laser-induced refractive index change technology intended to “overcome the safety and performance issues with existing refractive surgery, contacts lenses and IOL options,” according to the company’s website.

Spherical aberration and potentially other higher-order aberrations can be addressed with the refractive index changing techniques, as well as astigmatism and fine-tuning of a toric lens. A monofocal lens can be turned to multifocal and vice versa, and any refractive miss on accommodating lenses could potentially be adjusted at any time after implantation.

“If patients do not have the financial resources to treat astigmatism or to have a multifocal lens but may want to do it later in life, RIS would offer that option. They would not have to select that premium technology ahead of time and pay for it upfront. There is a lot of flexibility there. You can even look back at your patient population, those where you have already done a good job that still needs fine-tuning. This would be an option for them, and it might be even several years down the road from surgery,” Jones said.

As opposed to the LAL, there is no need to wear protective spectacles after the lens has been adjusted because there is no risk that light or other factors might alter the treatment. This spares a lot of anxiety to the patient and surgeon, Jones said.

With the LAL, he also noticed that having to dilate the patient multiple times within a short window — for adjustment, for checking the results and for the final lock-in procedure — leads to incomplete dilation. As a consequence, some areas of the optic may not be properly locked-in.

“There is a cumbersome nature of it in the clinic as well. You have multiple visits, and logistically and clinical resource-wise, there may be some challenges there. RIS is more straightforward. There are distinctive advantages over the LAL: no timing issue, fewer treatments, use any IOL. Flexibility is a key feature for being an acceptable product for patients,” Jones said.

Studies in humans are currently ongoing, and further refinements on energy delivery are underway.

“Once this technology becomes available, perhaps we will be able to achieve a level of specificity and accuracy that has never been achieved before with intraocular lenses,” Jones said. – by Michela Cimberle

• References:
• Alió JL, et al. J Cataract Refract Surg. 2012;doi:10.1016/j.jcrs.2012.05.027.
• Clerio Vision. cleriovision.com/about-us. Accessed July 5, 2019.
• Dhital A, et al. J Cataract Refract Surg. 2013;doi:10.1016/j.jcrs.2013.05.049.
• Femtosecond laser-induced refractive index change may lead to paradigm shift in refractive correction. www.healio.com/ophthalmology/refractive-surgery/news/print/ocular-surgery-news/%7Bea03f8aa-c2a6-4687-97a9-08df26873630%7D/femtosecond-laser-induced-refractive-index-change-may-lead-to-paradigm-shift-in-refractive-correction. Accessed July 5, 2019.
• Ford J, et al. J Cataract Refract Surg. 2014;doi:10.1016/j.jcrs.2014.05.005.
• Hengerer FH, et al. Ophthalmology. 2011;doi:10.1016/j.ophtha.2010.12.005.
• Hengerer FH, et al. Ophthalmology. 2011;doi:10.1016/j.ophtha.2011.05.030.
• Hovanesian JA. Clin Ophthalmol. 2018;doi:10.2147/OPTH.S182943.
• Kohnen T. J Cataract Refract Surg. 2011;doi:10.1016/j.jcrs.2011.10.005.
• Nguyen J, et al. J Cataract Refract Surg. 2018;doi:10.1016/j.jcrs.2017.09.036.
• Olson RJ. Am J Ophthalmol. 2018;doi:10.1016/j.ajo.2017.08.020.
• Page TP, et al. Clin Ophthalmol. 2016;doi:10.2147/OPTH.S101325.
• 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.

• For more information:
• Sumit “Sam” Garg, MD, can be reached at University of California, Irvine, 850 Health Sciences Road, Irvine, CA, 92697-4375; email: gargs@uci.edu.
• Jason Jones, MD, can be reached at Jones Eye Clinic, 4405 Hamilton Blvd., Sioux City, IA 51104; email: jasonjonesmd@mac.com.
• Jay S. Pepose, MD, PhD, can be reached at Pepose Vision Institute, 1815 Clarkson Road, Chesterfield, MO 63017; email: jpepose@peposevision.com.
• Vance Thompson, MD, can be reached at Vance Thompson Vision, 3101 W. 57th St., Sioux Falls, SD 57108; email: vance.thompson@vancethompsonvision.com.
• Gary N. Wörtz, MD, can be reached at Commonwealth Eye Surgery, 2353 Alexandria Drive, Suite 260, Lexington, KY 40504; email: 2020md@gmail.com.

Disclosures: Garg reports he serves on the medical advisory board of LensGen. Jones reports he is a consultant to Perfect Lens and Johnson & Johnson Vision and was in the past a consultant for Calhoun Vision. Pepose reports he is a consultant for AcuFocus, Bausch + Lomb and Johnson & Johnson Vision. Thompson reports he is a researcher and consultant for RxSight. Wörtz reports he is the founder and a shareholder of Omega Ophthalmics.

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