Quest for the perfect IOL

Presbyopia results from the loss of flexibility of the natural crystalline lens, which progressively limits its ability to change focus with age. So, replacing the sclerotic natural lens with an accommodating intraocular lens (AIOL) would seem the ideal solution to restore the full range of vision - at least in theory.

Even so, producing an AIOL that reliably provides sharp focus while minimising visual disturbances across a continuous range of near, intermediate, and far distances has proven difficult. The lens must be both stable enough to provide good base refraction yet sensitive enough to change power in response to minute accommodative impulses, said Dr Pablo Artal, who has patented a lens theoretically capable of accommodation yet to be tested. “It’s a daunting challenge,” he added.

AIOL-labelled lenses have been available in Europe for more than two decades, and they generally deliver a broader defocus curve than monofocal IOLs. And while they vary considerably in design, ACIOLs have been plagued by a variety of issues. These include durability and magnitude of effect; induction of dysphotopsias such as glare, halos, and starbursts; high rates of posterior capsule opacification (PCO); sizing issues; large insertion incisions; and even fundamental questions about their purported mechanisms of action.

Yet, the theoretical payoff is so great that the quest for improved AIOLs continues. And there’s progress, said Dr Thomas Kohnen. “There are several products which are promising at the moment.”

3.0 D+ accommodation for 36 months

Given the capsular bag’s tendency to fibrose and stiffen over time, whether lenses relying for accommodation on ciliary muscle contractions transmitted through the bag will function long-term is a significant question. Recently released 36-month results of the Juvene (LensGen) modular, shape-changing fluid-optic AIOL give a reason for optimism.

Among 18 eyes evaluated, including 10 in 5 bilaterally implanted patients, the mean distance-corrected monocular defocus curve was above 20/40 from approximately +1.5 D to -2.0 D. This roughly 3.5 D accommodative range yielded mean distance-corrected visual acuity (VA) values of 20/18 at 4 m distance, 20/32 at 60 cm intermediate, and 20/44 at 40 cm near, Dr Sumit Garg reported at the 2023 ASCRS annual meeting. “You get uninterrupted vision from distance to intermediate to near,” he said, noting binocular results were even better.

Both the 36-month monocular and binocular results were very similar to or even a bit better than the 12- and 24-month results, though many patients were lost to follow-up over time due to COVID, non-IOL-related adverse events, and death (unrelated to the IOL). Mean uncorrected manifest refractions were also stable over 36 months. The durability of the refractive and accommodative results speaks to the effectiveness of Juvene’s bag-filling design, which has shown low PCO rates with good stability in both clinical and animal studies. “It’s very gentle; we are not seeing any zonular instability, no pseudophacodonesis, or PCO,” Dr Garg said.

Juvene also provides mesopic contrast sensitivity similar to a monofocal IOL. “We talk about range of vision and quality of vision but not both at the same time,” he said. “A lens like this allows us to do both at the same time.” The results are good enough to win approval from the FDA for a pivotal trial. LenGen is currently raising money to pay for it.

Another AIOL demonstrating a subjective accommodative amplitude of about 3.0 D above 20/25 is the Lumina (Akkolens). A custom-sized lens implanted in the sulcus, it consists of two optical elements that slide across each other under accommodative effort. The lens has retained its accommodative range for up to 3.3 years, Professor Jorge Alió reported at the 2022 ESCRS Congress in Milan. A company statement said the Lumina is CE marked and will soon be commercially available at select outlets in Europe.

Also in clinical trials is the FluidVision (Alcon)—a flexible hydrophobic acrylic body filled with silicone oil. Fluid squeezed from peripheral reservoirs changes the lens’s shape to reportedly achieve about 2.2 D of objective accommodation. The lens fills the capsular bag and shows very low PCO rates.

The OmniVu (Atia Vision) is a modular shape-changing IOL with a fixed anterior optic and a fluid-filled, shape-changing base. The lens base is also designed to fill the capsular bag, and both components contain refractive power. Preliminary results from the first-in-human trial involving 25 eyes in 18 patients (9 implanted bilaterally, 9 with the OmniVu in just one eye) showed a mean 20/20 monocular uncorrected distance vision six months after implantation, 20/25 intermediate, and 20/32 near, Dr George O Waring IV reported at the 2023 ASCRS annual meeting. Ninety-five percent of eyes were within 0.5 D of plano at six months. For patients with the OmniVu lens implanted bilaterally, binocular uncorrected vision averaged 20/16 distance, 20/20 intermediate, and 20/32 near.

7.0 D accommodation in development

Nonetheless, replicating the accommodative amplitude of the young adult eye requires more than a 3.0 D range. Providing a full range of vision requires about 7.0 D to maintain a 50% reserve for sustained near focus, said paediatric ophthalmologist Dr Forrest J Ellis. The JelliSee lens he developed may deliver.

The JelliSee lens is an in-the-bag, fluid-filled AIOL with a fixed power posterior surface and a nearly flat, flexible, curvature-changing anterior surface. The anterior surface diameter increases slightly when the ciliary muscles relax. The force is transmitted by eight haptic arms attached near the anterior surface perimeter, mimicking the attachment points of the zonules to the natural lens. Placing these attachment points just 500 microns anterior to the lens equator increases dioptric power change five-fold, Dr Ellis said.

Mathematical modelling suggests this lens can achieve more than 7.0 D accommodative amplitude with less than 0.2 mm diameter change with excellent image quality across the range, which is within the range of movement available with an older capsule. Lab tests confirmed these theoretical results, and a primate model demonstrated 7.0 D of accommodative amplitude 15 months after implantation, he said.

These promising results appear to be holding up in first-inhuman pilot studies. One day after JelliSee lens implantation in a 59-year-old female, she was reading 20/16-3 at distance and 20/25 ultra-near at 20 cm, both with distance correction for astigmatism, Dr Ellis reported. Similarly, six months after implantation, a 69-year-old male read 20/25-2 at distance, 20/25-3 at near 40 cm, and 20/25 ultra-near at 20 cm uncorrected, with a manifest refraction of +0.50 D, -0.75 x 45. “We actually had to blow the [ultra-near] vision chart up because no one could see what he was reading,” he said.

Dr Ellis is confident the mechanism will hold up, noting the ciliary muscle has been shown to continue contracting in patients well into their 80s. The lens’s haptic actuators are designed to scar into the lens capsule periphery, and it actually gained accommodative amplitude as the capsule fibrosed in the primate model, he reported. “Fibrosis is actually our friend.”

Premium lenses for more

A big advantage of AIOLs is their image quality makes them potentially suitable for many more patients than multifocal lenses, Dr Garg said. “It’s non-diffractive, so you are not losing any luminance to the retina and don’t have to worry about glaucoma or retina or whatever it is—you can still give them some range of vision.”

Dr Ellis agreed. “An accommodating IOL is possible: one that can provide excellent quantity of vision, excellent quality of vision, a full range of dioptric powers, and can be placed in the bag through a small incision.”

Still, several challenges remain, among them choosing a proper A constant to determine lens base power. Lens durability also remains an open question. Only more time and testing will tell.

“It’s a long journey, it’s innovation,” Dr Kohnen said. “We will get there, but I don’t know when.”

Pablo Artal PhD is professor of physics, specialising in optics at the University of Murcia, Spain. pablo@um.es

Thomas Kohnen MD, PhD, FEBO is professor and chair, Department of Ophthalmology, Goethe University, Frankfurt, Germany, and ESCRS treasurer. kohnen@em.uni-frankfurt.de

Sumit Garg MD is professor of ophthalmology at the University of California, Irvine, US, and serves on the scientific advisory board of LensGen Inc. gargs@uci.edu

Jorge L Alió MD, PhD is professor and chairman of ophthalmology at Miguel Hernández University of Elche and Founder of Vissum Miranza in Alicante, Spain. jlalio@vissum.com

George O Waring IV MD is founder and medical director of the Waring Vision Institute, Mt Pleasant, South Carolina, US. gwaring@waringvision.com

Forrest J Ellis MD is a paediatric ophthalmologist and founder and CEO of JelliSee Ophthalmics, McLean, Virginia, US. jim@jellisee.com