Presbyopia treatment options now and on the horizon

Refractive
September 2021

by Ellen Stodola
Editorial Co-Director

Dr. Waring implants a hybrid diffractive extended depth of focus and multifocal toric IOL during a refractive lens exchange. Source: George Waring IV, MD, FACS
Dr. Waring implants a hybrid diffractive extended depth of focus and multifocal toric IOL during a refractive lens exchange.
Source: George Waring IV, MD, FACS

The large number of patients worldwide with presbyopia creates a unique opportunity for eyecare providers to improve patients’ quality of life, according to George Waring IV, MD, FACS. There are more than 2.1 billion presbyopes worldwide. Dr. Waring noted the many implications of this large number, not just from a quality of life standpoint but also in terms of economic burden related to falls. Many falls are related to bifocal glasses, Dr. Waring said, which most people with presbyopia require at some point in their life.

“Our discussions and surgical decision making regarding presbyopia are framed in terms of dysfunctional lens syndrome,” which Dr. Waring said is a characterization of the aging process of the internal crystalline lens. Stage 1 is presbyopia; stage 2 is presbyopia and early lens opacity; and stage 3 is a cataract affecting daily activities adversely. “We have proposed an algorithm for the treatment of presbyopia based on age, refractive status, and lens opacity,” he said.1,2

Dr. Waring said treatment options are largely dictated by patients’ refractive status, meaning if they’re hyperopic and the higher the degree of hyperopia, the earlier a lens-based intervention procedure may be recommended.

“The more myopic they are, we may have a higher threshold to do a lens-based procedure, maybe even a lens replacement procedure, and a lower threshold for a cornea-based procedure or implantable contact lens,” he said.

For the plano presbyope, Dr. Waring said they are moving toward a lens-based procedure to maintain binocularity, which he thinks improves vision performance and may lead to higher patient satisfaction.

“When considering age, once pharmacologic therapies are approved for the treatment of presbyopia, we may initially recommend that as an alternative to glasses and contacts,” Dr. Waring said. “However, as patients move through various stages of lens dysfunction, in the context of their refractive errors and/or desires, then we would look at surgical interventions.”

Surgical options

Shamik Bafna, MD, said he tends to break down the treatment options for presbyopia by what is accessible in the U.S. and what’s available outside the U.S. “In the U.S., there are modalities that you can employ within the cornea and modalities to employ within the lens,” he said.

Within the cornea, Dr. Bafna said the most common option is monovision. PRK, LASIK, or SMILE can be used where you take the non-dominant eye and under correct a little to give near vision and correct the dominant eye for distance vision, he explained.

Most patients like monovision quite a bit, but the main drawback is it’s not a long-term solution. “You’re dealing with presbyopia, which continues to progress,” Dr. Bafna said. “Someone may be able to read initially, [but] they may lose near vision over time and have more intermediate vision when the presbyopia gets worse.”

Monovision works well for patients in their 40–50s. For those in their late 50s–60s, monovision doesn’t work as well, he said.

In the past, many people would defocus the near eye, Dr. Bafna said, to a target of –2 to –2.5 D. Over time, they realized that creates too much anisometropia, and patients don’t like losing that much distance vision in the near eye. They lose more depth of field and depth of focus because the eyes aren’t working together.

These days, he said patients prefer –1.25 to –1.5 D, so there’s less difference between the two eyes. This is better tolerated by patients and there’s not as much loss of distance vision.

With monovision there is some compromise associated; you have to give up distance vision to get near vision and vice versa. “When we target monovision, we try to simulate it with a contact lens trial to make sure a patient likes it,” Dr. Bafna said.

While monovision is one of the most popular options within the U.S. for presbyopia correction, another strategy Dr. Bafna’s practice employs is an inlay, specifically the Kamra (AcuFocus). He explained how Kamra increases the depth of field using small aperture optics. “You don’t sacrifice as much distance vision in the near eye as when you do traditional monovision.” However, there is not a lot of market demand for the inlay, he said.

Another inlay is the Flexivue Microlens (Presbia), which completed an FDA trial and is being analyzed. Dr. Bafna was involved in this clinical trial.

He also mentioned allografts, which use actual corneal tissue instead of a foreign body. These options are still in development or not yet available in the U.S.

An inlay from Allotex, which is undergoing FDA trial for near vision, is placed superficially in the cornea with the idea that you want to change the curvature of the non-dominant eye to allow it to focus near. This option is made from human tissue that has been cryopreserved.

Soosan Jacob, MD, has introduced a similar idea. Her technique is called the presbyopic allogenic refractive lenticule (PEARL), which uses leftover corneal lenticular tissue removed in a SMILE procedure. There is a process to make sure there are no issues with the tissue; a small button is taken out and cryopreserved to use in another patient’s eye, Dr. Bafna explained.

From a corneal perspective, Dr. Waring mentioned the blended vision approach with LASIK and/or PRK and with implantable contact lenses. He also said that there are new scleral treatments in development. He serves as the director of the Scientific Advisory Board for the new Laser Scleral Microporation procedure (LSM, Ace Vision Group), which he said is showing promise in early human trials. This is a minimally invasive presbyopia surgical procedure designed to naturally restore function.

There are several other surgical procedure options available outside the U.S., Dr. Bafna said, mentioning presbyLASIK, PRESBYOND (Carl Zeiss Meditec), and INTRACOR used internationally.

PresbyLASIK creates a multifocal cornea, Dr. Bafna said. “It’s an attempt to replace the dynamic process of accommodation with static modification of the corneal surface,” he explained, noting that this is primarily for patients who are low hyperopes. It’s not used that frequently, he said, due to the loss of contrast sensitivity it creates and reduction in distance vision.

With INTRACOR, instead of creating a flap, a femtosecond laser is used to change the overall curvature of the cornea, Dr. Bafna said. With this, concentric rings are created inside the interior of the cornea to steepen the curvature of the small central zone, adding power and increasing depth of focus. Dr. Bafna said the process is intriguing because it’s less invasive overall, but he noted compromises, like loss of contrast sensitivity and the potential for night vision disturbances.

Dr. Bafna said that PRESBYOND is used a fair amount outside the U.S., and he wishes it was available here.

When you do excimer ablation, the goal is to reduce spherical aberration because it helps patients to see more crisply at a particular point of focus, Dr. Bafna said. If you increase spherical aberration, it increases depth of field. PRESBYOND uses the concept of increasing spherical aberration with proprietary ablation techniques that increase overall spherical aberration on the cornea. It also has an element of monovision that helps increase the depth of field and gives patients near and distance vision.

Dr. Bafna noted that PRESBYOND is different from traditional monovision because it’s blended vision. The distance vision is good, there is decent intermediate, and the near eye gets more intermediate and more near. There’s not too much difference between the two eyes.

Lastly, Dr. Bafna discussed lens-based options. “What’s nice about working at the lens level is you’re going where the problem is. When you try to correct it at the corneal level, you’re not focusing where the problem is,” Dr. Bafna said, explaining that as the lens continues to get worse, cornea-based options lose more of their effect.

With lens-based options, you either wait for the patient to develop a cataract or you perform a refractive lens exchange before a cataract develops, he said.

There are a lot of different lenses in development, Dr. Bafna said. Surgeons currently have access to multifocal and extended depth of focus lenses. “In the past, most multifocal lenses we employed were bifocal lenses,” he said. “When PanOptix [Alcon] got approved in the U.S., that changed things to where we got to the same level as the rest of the world.” He added that more trifocal lenses are being developed, and these tend to be more effective, covering distance, intermediate, and near vision. The main downside of multifocal lenses is they use a diffractive optic that splits light, so patients will have some dysphotopsia, especially at night. As the technology has improved, the amount of dysphotopsia has been reduced, he added.

Extended depth of focus lenses include the Symfony (Johnson & Johnson Vision) and Vivity (Alcon). Symfony has a diffractive optic, which could have some degree of dysphotopsias, and it doesn’t give as much near vision, Dr. Bafna said.

“What’s unique about Vivity is it’s the first and only non-diffractive IOL, so it does not split light,” Dr. Bafna said. “It has a dysphotopsia profile that’s similar to other monofocal lenses and gets distance and intermediate and some functional near while avoiding dysphotopsia.”

Dr. Waring said he thinks one of the most exciting areas of presbyopia surgery is lens replacement procedures. “We now have femtosecond lasers, which are intuitive to patients looking for laser vision correction,” he said. There is also a selection of presbyopia-correcting refractive implants that can really deliver on both quantity and quality of vision, he added, as well as a rich pipeline of implants in development that have great promise.

“We think of presbyopia as one of the emerging subspecialties within the specialty of refractive surgery and refractive cataract surgery,” Dr. Waring said, adding that a large portion of his practice is dedicated to the art and surgical management of presbyopia. He said there are more diagnostics geared toward diagnosing the different stages of the dysfunctional lens, which will help clinicians make a better decision in terms of what type of treatment is appropriate.

Pharmacological options

Another presbyopia treatment in development is the use of eye drops, though no product is currently approved by the FDA.

Dr. Waring served as the principal investigator for the Allergan clinical trial for a novel eye drop for the treatment of presbyopia. If approved, it will be the first eye drop to help reduce dependence on reading glasses and contact lenses for the treatment of presbyopia.

He said there are a number of other drops in development as well, though other products are earlier in the development process than the Allergan one.

“These drops will likely serve as a gateway to help the public and eyecare providers understand what presbyopia is,” he said. “It is a naturally ubiquitous condition that can be helped, and they will have an alternative to reading glasses, bifocals, and contact lenses. These could be perfect for those that are recently experiencing the earlier stages of lens dysfunction.”

Dr. Bafna highlighted the eye drops under investigation, primarily in clinical trials. Some of them are based on the concept of pupil constriction, which increases the overall depth of field. The idea is that patients will only have to apply drops once or twice a day.

Dr. Bafna said the drops look promising overall. For patients who want a stop gap measure between glasses or contacts and a surgical procedure, he thinks these drops are a good noninvasive methodology.

ARTICLE SIDEBAR

Presbyopia eye drops in development

AGN-190584 (Allergan): AGN-190584 (pilocarpine 1.25%) was tested in two Phase 3 clinical studies, GEMINI 1 and GEMINI 2, where the primary endpoint was met. According to the company, AGN-190584 is “an investigational optimized formulation of pilocarpine, a cholinergic muscarinic receptor agonist, which activates muscarinic receptors located at smooth muscles such as the iris sphincter muscle and ciliary muscle and is being investigated for the treatment of presbyopia as a topical, once-daily drop delivered by a proprietary vehicle.” According to Allergan, “the proposed mechanism of action of AGN-190584 is through contraction of the iris sphincter muscle, constricting the pupil to enhance the depth of focus and improve near and intermediate visual acuity while maintaining some pupillary response to light. AGN-190584 also contracts the ciliary muscle, facilitating accommodation.”

MicroLine (Eyenovia): This product is a pilocarpine solution administered with the company’s Optejet dosing instrument. In June 2021, the company announced results from the Phase 3 VISION-1 clinical trial, which met its primary endpoint.

Nyxol (Ocuphire Pharma): According to the company, “Nyxol is a preservative-free ophthalmic solution containing 0.75% phentolamine (or 1% phentolamine mesylate), a nonselective alpha-adrenergic antagonist that inhibits the contraction of smooth muscle of the iris.” It is currently being developed under the 505(b)(2) pathway for dim or night vision disturbances, reversal of pharmacologically induced mydriasis, and presbyopia. The company stated, “Phase 2 trials showed reduced pupil diameter, resulting in better contrast sensitivity and visual acuity.” Enrollment in the VEGA-1 Phase 2 clinical trial was completed in May 2021, and the company was issued two patents related to the product in May.

CSF-1 (Orasis Pharmaceuticals): CSF-1 is meant to repurpose existing and well-studied molecules, according to the company. Two Phase 3 clinical studies, NEAR-1 and NEAR-2, were initiated in October 2020.

PRX-100 (Presbyopia Therapies): According to the company, this product is “based on discoveries combining a proprietary vehicle with unique miotic combinations, without using pilocarpine. The drops are intended to induce strong miosis to create a significant pinhole effect with a depth of field enhancement, without any associated accommodative distance blur. PRX was developed to compliment current treatment options (not a permanent replacement for reading glasses, contact lenses or other options) and is reversible.”

BRIMOCHOL (Visus Therapeutics): According to the company, “BRIMOCHOL is a proprietary pupil-modulating eye drop that combines two well-studied, FDA-approved pharmaceuticals: carbachol (a cholinergic agent) and brimonidine tartrate (an alpha-2 agonist). Together, they produce a ‘pinhole effect,’ which reduces the size of the pupil so that only centrally focused light rays are able to enter the eye, thereby sharpening distant and near images while minimizing side effects. The result is clarity of vision for near tasks like reading or using a smartphone.” In March 2021, the FDA accepted an Investigational New Drug application for BRIMOCHOL, and the company announced the commencement of a Phase 2 clinical trial later that month.

*This is not an exhaustive list, and there may be other presbyopia eye drops in development.


About the physicians

Shamik Bafna, MD
Cleveland Eye Clinic
Brecksville, Ohio

George Waring IV, MD, FACS
Waring Vision Institute
Mt. Pleasant, South Carolina

References

  1. Waring GO, Rocha KM. Characterization of the dysfunctional lens syndrome and a review of the literature. Curr Ophthalmol Rep. 2018;6:249–255.
  2. Mercer RN, et al. Future trends in presbyopia correction. J Refract Surg. 2021;37:S28–S34.

Relevant disclosures

Bafna: Alcon, CorneaGen, Carl Zeiss Meditec
Waring: Ace Vision Group, Allergan, Johnson & Johnson Vision

Contact

Bafna: drbafna@clevelandeyeclinic.com
Waring: gwaring@waringvision.com