Temporary, permanent solutions expand choices for presbyopia correction
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Few visual impairments have as far a reach as presbyopia.
According to a 2018 study published in Ophthalmology, the global prevalence of presbyopia was about 25% in 2015. That is nearly 2 billion people with presbyopia across the world.
Source: Stefania Verastegui
“Anyone over the age of 40 can start to have symptoms of presbyopia,” OSN Technology Board Member Jennifer M. Loh, MD, said. “We know that it’s affecting a huge population in our country, as well as globally. There’s actually evidence that people who do not have their presbyopia corrected, whether by glasses or some other means, have a decreased quality of life due to difficultly performing everyday tasks.”
At the clinic level, surgeons see firsthand the burden of presbyopia and how many people it affects.
“With an aging population, eventually we could have over a third of the population with presbyopia,” OSN Presbyopia Board Member Luke Rebenitsch, MD, said. “There has been a realization that there’s huge potential in this space because we have well over 100 million people who are presbyopic in this country, and that number has only been growing.”
The practice that Rebenitsch joined was mainly a LASIK practice until about 7 years ago when it started adding refractive lens exchange and blended vision. While LASIK has remained steady, he said lens exchange has seen rapid growth.
“Lens exchange alone has grown about 30% per year for the last 5 years,” he said. “I don’t know how big it is going to get, but so far, it hasn’t stopped.”
For many years, the main solutions for presbyopia had been glasses and contact lenses. Loh said another common option is laser vision correction to create monovision.
“That’s actually been very successful, but it does come at a cost,” she said. “Because we’re inducing monovision, there is a loss of stereopsis. As low as 0.75 D of monovision is enough to cause loss of depth perception. They say there’s no such thing as free lunch, but overall, LASIK or laser vision correction has been successful.”
Presbyopia has gained more attention since Vuity (pilocarpine hydrochloride ophthalmic solution 1.25%, Allergan) was launched in 2021 as the first FDA-approved drop to treat the condition. Nandini Venkateswaran, MD, said the drop has created a lot of excitement for patients and physicians.
“I feel empowered to talk about presbyopia and initiate conversations with my patients because my armamentarium for therapeutics has continued to grow,” she said. “The launch of Vuity has stirred up a lot of interest, and we’ve seen the presbyopia landscape really grow. We have so many companies coming out with different drops that are harnessing pupillary constriction or lens softening to help patients gain more presbyopia correction.”
Treatment options
Since its approval, Vuity has continued to demonstrate positive results in patients with presbyopia. In a study presented at the American Academy of Ophthalmology meeting in Chicago, Beeran B. Meghpara, MD, and colleagues evaluated visual acuity responses to Vuity at 30 days using pooled data from the phase 3 GEMINI studies.
In the studies, 750 patients with presbyopia were randomly assigned to receive Vuity or vehicle once daily for 30 days, and distance-corrected near visual acuity was assessed under mesopic and photopic conditions.
More than 39% of emmetropes in the Vuity group achieved at least three lines in distance-corrected near visual acuity compared with less than 14% in the vehicle group (P < .0001). Among hyperopes, the percentages were 33.3% vs. 12.5%, which was not a statistically significant difference, while among myopes, the percentages were 46.9% vs. 9.8% (P = .0002).
Other presbyopia drops are also in development. In October, Lenz Therapeutics reported positive topline data from the phase 2 INSIGHT trial that investigated two formulations, LNZ100 (aceclidine) and LNZ101 (aceclidine plus brimonidine).
Both formulations met the primary endpoint of near visual acuity improvement of at least three lines without losing one line or more in distance visual acuity at 1 hour. In the LNZ100 group, 71% of patients met the primary endpoint compared with 6% in the vehicle group. Additionally, 56% of patients in the LNZ101 group met the primary endpoint. The effect was lasting, with 37% of patients in the LNZ100 group and 48% of patients in the LNZ101 group maintaining at least three lines of improvement compared with vehicle at all of the study’s timepoints, including up to 10 hours.
Based on these results, Lenz Therapeutics plans to continue studying the formulations in phase 3 trials.
Loh said drops have a role in the treatment of presbyopia, but they are not a perfect solution.
“The advantage is the fact that it’s not surgery — it’s reversible,” she said. “However, there are also issues. It’s not permanent, so people have to keep using them, and they don’t last all day. Not everyone is a candidate, either. It depends on their prescription, and there are things we have to look out for to make sure it’s a good fit. It’s not a 100% panacea.”
For all of the excitement that an approved drop brought, Rebenitsch has found that, at least in practice, it is not for everyone.
“It’s worked in some patients, but there are a number of patients where it didn’t work as well,” he said. “It can be annoying for some patients to take regularly. What we’ve found is that at least 50% to 70% of patients who come in our doors are looking for a permanent solution.”
Refractive surgery is a permanent solution for presbyopia, but Loh said it is all about finding the right patient. She said drops will generally work better in patients with plano vision or a small refractive error. When working with some patients who have more than 1 D of hyperopia, she said they may not get enough power for reading. It can also be age dependent. Myopia presents different issues, including retinal concerns, that might not make those patients a good match for drops and steer them toward surgery.
“It’s almost like you have to have a patient right in that sweet spot,” she said. “If they’re older, they typically have less accommodation, so they would get less benefit from the drops, which provide about up to three lines of improvement in near vison.”
While someone starting from a worse baseline vision might not benefit from those three lines, refractive lens exchange lets them have a clean slate, Loh said.
“You’re taking away their current refraction, and you’re able to make them plano with a presbyopic lens,” she said. “Presbyopic IOLs provide a range of vision, or surgeons can target mini-monovision with monofocal or toric IOLs. With drops, you’re still working with the eye’s natural ability, whereas refractive lens exchange is resetting the template.”
Venkateswaran said there is a broad selection of options for patients with presbyopia based on a range of technologies. Choosing the right option comes down to stages of life and the condition.
“You really have to triage patients based on their age and what stage of presbyopia they are in,” she said. “You have patients who are 40 years old who are just starting to notice a change in their reading vision. They might be having a little bit of crystalline lens dysfunction but can still shine with readers, contact lenses or presbyopia drops. If they are particularly motivated, they are great candidates for laser-based surgery with a monovision or blended vision target.”
However, as patients start to reach ages 55 years and older and enter “absolute presbyopia,” lens-based surgery becomes the better option.
“These are the patients who have really lost the majority of the accommodative capacity of their crystalline lens,” she said. “They are going to get the most bang for their buck by harnessing our new lens technologies and figuring out which one will give them the range of vision that they need for their daily visual needs.”
For patients looking for a permanent solution, Rebenitsch said the introduction of premium IOLs such as trifocal lenses has been a major addition to the refractive tool kit.
“The defocus curves are a lot flatter, so we don’t typically have to give up as much,” he said. “You can see seamlessly from distance to near without any drop-off.”
Custom lens replacement
The latest IOL technologies allow surgeons to customize a patient’s visual range. OSN Presbyopia Section Editor George O. Waring IV, MD, FACS, said one of the purest indications for lens-based presbyopia surgery is in plano presbyopes, who have historically been some of the hardest patients to treat.
“For hyperopes, including latent hyperopes, the more hyperopic, the younger we tend to recommend lens replacement and the more straightforward the indication. With the plano presbyope, however, we tend to reserve lens replacement for the second stage of lens dysfunction, where the uncorrected near visual acuity has really taken a turn for the worse, and distance quality may be affected by aberrations and early opacity,” Waring said.
“The beauty of custom lens replacement is that it not only fixes the problems you were born with, like focus problems, but it also fixes your age-related issues,” he said. “You’re getting to the source of the problem, which is typically the right thing to do.”
Waring said lens replacement can also help patients maintain balanced vision and restore depth perception.
“It’s anti-aging in its purest form,” he said. “Your lens can’t become increasingly dysfunctional when you have a restorative implant. For all of those reasons, this has become one of the most popular and rapidly growing segments of our practice.”
When proceeding to lens replacement, Waring said there needs to be a careful discussion with the patient about balancing the risks and benefits and, as importantly, setting expectations.
“We are careful to make distinctions about the visual journey that they’ll go on as their brain accommodates to the implant,” he said. “This is not the same as what they had early on in life, nor is it the same as putting on glasses or contact lenses.”
There are several lens options for patients with presbyopia, and Venkateswaran said selecting the right lens is based on what the patient needs in their day-to-day life. For patients who desire a wide range of vision, she said she has a lot of success with the PanOptix trifocal lens (Alcon).
“Patients who want trifocality are very active and want to do 90% to 95% of daily activities without glasses,” she said. “They’re willing to take on the small risk of glare and halos at night but also understand that they still may need glasses to read small print or see in dim light setting. But they really want to live an overall spectacle-free life.”
For patients who are not as motivated for full range of vision, Venkateswaran uses an extended depth of focus lens such as the Tecnis Symfony (Johnson & Johnson Vision) or the Vivity (Alcon).
“These work best in patients who might do more distance and computer work and want to be glasses-free at those ranges,” she said. “I also like to use them in patients who have previously undergone keratorefractive surgery because they are more forgiving in these altered corneas. Lastly, the non-diffractive nature of the Vivity lens provides a reduced glare and halo profile, which is desirable for a subset of patients.”
One of the more recent additions to the presbyopia lens family is the IC-8 Apthera small-aperture IOL (AcuFocus). Similar to presbyopia drops, Loh said the IC-8 creates a pinhole effect, giving patients up to a 3 D range of focus. In situations that call for monovision, Loh said she has also had success with the Light Adjustable Lens (RxSight).
“We have many technologies at our disposal,” she said. “Not every IOL is perfect for every candidate, but we certainly have many options to offer to patients.”
Future treatments
Even with the massive uptick in custom lens replacement for presbyopia, Waring said he expects it to grow further. The need for tailor-fit lenses will also require new technology and improved implants.
Waring said he is particularly excited about accommodating and modular IOLs such as the Atia Vision IOL, which has a dual lens that allows for future refractive corrections.
“It has a fluid-filled, shape-changing base that’s designed to simulate the natural accommodative mechanism,” Waring said. “Then, it has a fixed-power front optic that is customizable for the target refraction and can be changed in the future. Early clinical data are showing extraordinarily robust depth of focus curve and quality of vision.”
Waring said another promising accommodating IOL on the horizon is the Juvene (LensGen).
“Twelve-month results from the Grail study showed desirable visual outcomes and good safety data,” he said. “It has a circumferential haptic and a fluid lens that fits in the base and simulates accommodation.”
Waring said there has been innovation beyond the IOL space as well, including a scleral laser system being developed by Ace Vision Group.
“It utilizes a laser to create microporations selectively over the sclera,” he said. “In doing so, it basically de-cross-links the area to favorably affect biomechanical properties in a focal fashion over the sclera that is shown to restore accommodation while preserving the natural optical profile of the cornea and the internal lens.”
Ultimately, Waring said procedures like this have the potential to become “lunchtime” laser vision correction types of procedures, creating their own category, “MIPS,” or minimally invasive presbyopia surgery.
Rebenitsch said even with innovations such as Vuity and all of the IOL options on the market, the presbyopia space is only getting started.
“This is a space is in its infancy in terms of pharmacologic and surgical management,” he said. “Especially for refractive practices, we don’t want to miss the potentially millions of patients out there who want solutions.”
The biggest unmet need in surgical correction of presbyopia is a lens that does not come with any compromises. Loh said she is looking forward to a lens that can provide a full range of vision without dysphotopsias or other side effects.
“That’s always the double-edged sword, especially with presbyopic IOLs that provide a board range of vision,” she said. “It seems like there’s always some sort of compromise. In a perfect world, we would have a lens that did not induce halos or glare but also gave a full range of vision, which is what patients are looking for.”
For now, each surgeon has to make the right choice for each patient, whether it is an IOL or a drop.
“Each of us has a paradigm that we use to figure out which patients will benefit best from a particular IOL,” Venkateswaran said. “We’re going to have to do the same for presbyopia therapies. We need to further evaluate the clinical trials and apportion our patients to the right category of presbyopia-correcting therapy.”
- References:
- Fricke TR, et al. Ophthalmology. 2018;doi:10.1016/j.ophtha.2018.04.013.
- Meghpara BB, et al. Efficacy of pilocarpine HCl ophthalmic solution 1.25% in emmetropes and nonemmetropes in the 30-day GEMINI 1 and GEMINI 2 studies. Presented at: American Academy of Ophthalmology meeting; Sept. 30-Oct. 3, 2022; Chicago.
- Lenz therapeutics announces positive topline data from phase 2 INSIGHT trial of LNZ100 and LNZ101 to treat presbyopia. https://lenz-tx.com/2022/10/lenz-therapeutics-announces-positive-topline-data-from-phase-2-insight-trial-of-lnz100-and-lnz101-to-treat-presbyopia/. Published Oct. 18, 2022. Accessed Dec. 1, 2022.
- For more information:
- Jennifer M. Loh, MD, can be reached at Loh Ophthalmology Associates, 8585 Sunset Drive, Suite 201, Miami, FL 33143; email: jenniferlohmd@gmail.com.
- Luke Rebenitsch, MD, can be reached at ClearSight LASIK, 7101 NW Expressway, Suite 335, Oklahoma City, OK 73132; email: dr.luke@clearsight.com.
- Nandini Venkateswaran, MD, can be reached at Massachusetts Eye and Ear Waltham, 1601 Trapelo Road, Suite 184, Waltham, MA 02451; email: nandini.venkat89@gmail.com.
- George O. Waring IV, MD, FACS, can be reached at the Waring Vision Institute, 735 Johnnie Dodds Blvd., Suite 101, Mt Pleasant, SC 29464; email: gwaring@waringvision.com.
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