Answering the Call of Presbyopic Patients

An estimated 1.8 billion people worldwide are presbyopic,¹ and more than 111 million of them live in the United States.² Of this large population of presbyopes, it is estimated that only 62% see an eye care practitioner each year.³

The number of presbyopes is expected to rise as the first of the millennial generation (born 1981 to 1996) begin to turn 40 this year. The US millennial population is estimated at 73 million, surpassing the size of the baby boomer population, which was estimated to be 72 million in 2019.⁴ As these aging millennials are added to the 61 million people who make up Generation X (ages 40 to 55), the total number of presbyopes requiring vision correction will increase substantially.

In a recent survey of people aged 40 to 55, 90% of respondents said they were frustrated with their presbyopia.⁵ Another survey found that, although 79% of respondents said they asked their eye care professional about issues concerning their near vision, 48% left without any discussion of their presbyopic needs.⁶ An estimated 32.6 million American adults wear over-the-counter readers,⁷ purchasing about 51.2 million pairs a year.⁸

Patients need and want more education about presbyopia, and optometrists are their trusted advisors for delivering this information. It is thus important to have intentional conversations with patients about their condition, the choices available for treatment (eg, eyeglasses, contact lenses, refractive surgery, and presbyopia-correcting IOLs), and how we can help them choose the best option or options for their needs.

MENU OF OPTIONS

When our patients become presbyopic, we can offer them multifocal eyeglasses or contact lenses, or we can discuss the option of refractive surgery. However, each of these solutions is associated with some sort of compromise. Patients’ different visual demands require customization, and the more tools we have in our arsenal the more we can help these patients live their best lives. After all, the goal is for patients to go about their lives without thinking about their eyes or feeling old or tired.

More tools for our arsenal are on the way, particularly in the form of presbyopia-correcting medications that affect the pupil in some way—chiefly by reducing pupil size to take advantage of the pinhole effect. Before we review those, here’s a quick refresher on pinhole optics.

Pinhole Optics

The pinhole effect is something we use every day in the clinic. When a pinhole is placed at the spectacle plane, it improves vision, but it also greatly reduces peripheral vision—not an ideal vision-correction solution. When the pinhole is moved to the iris plane, however, the result is extended depth of focus without restriction of peripheral vision. Leveraging the iris to create pinhole optics is therefore a viable option for improving near vision without degrading distance vision.

The next question is, “What is the ideal pupil size?” As it turns out, there is not one best pupil size. If the pupil is too big, near vision remains blurry. If the pupil is too small, distance vision becomes degraded. Optimally, a presbyopia solution that relies on pupil size reduction must provide good near vision without worsening distance vision. Xu et al found that the optimal pupil size may be a ratio, rather than a specific diameter: that is, a 40% to 50% reduction from the natural pupil size (Figure).⁹

Presbyopia-Correcting Medications

Several companies are developing presbyopia-correcting eye drops.

Allergan, an AbbVie company, has an investigational presbyopia-correcting eye drop in development. Two phase 3 trials, GEMINI 1 and GEMINI 2, are evaluating the drop’s safety and efficacy in study participants with presbyopia. Pilocarpine 1.25% had the longest duration of statistically significant 3-line improvement and the greatest mean improvement in UNVA letters at day 28.¹⁰ Allergan announced positive top line results of GEMINI 1 and 2, which will be the basis for a new drug application submission to the FDA in the first half of this year.¹¹

Eyenovia has a microdose drug delivery device (Optejet) that the company says can deliver a precise 7 μL dosage of pilocarpine that adheres uniformly to the ocular surface with an effect that lasts 3 to 4 hours.¹²

Ocuphire Pharma is enrolling patients in a phase 2 clinical trial, VEGA-1, to investigate its preservative-free ophthalmic solution (Nyxol) containing 0.75% phentolamine or 1% phentolamine mesylate, a nonselective alpha adrenergic antagonist that inhibits the contraction of the smooth muscle of the iris, for correction of presbyopia.¹³

PRX-100 (aceclidine, Presbyopia Therapies) is in phase 2b clinical trials. The active ingredient in this presbyopia-correcting drop is a parasympathomimetic miotic agent that acts on the muscarinic acetylcholine receptor.

CSF-1 (Orasis Pharmaceuticals) is a parasympathomimetic miotic also in phase 3 clinical trials. It has been shown to provide statistically significant improvement in near visual acuity of 3 lines or more.¹⁴

Brimochol (Visus Therapeutics) is a proprietary combination of carbachol and brimonidine tartrate designed to restore the loss of near vision associated with presbyopia. Five clinical studies have been conducted evaluating the safety and efficacy of the drop. In the most recent study of 57 patients, the drug demonstrated gains of 5 Jaeger lines or better, a statistically significant improvement in near visual acuity, with an effect lasting at least 12 hours.¹⁵ Phase 2 trials are slated to begin early this year.

OSRX Pharmaceuticals is developing two drops. One, called EyeFocus, contains pilocarpine HCl 0.302%, phenylephrine HCl 0.624%, pheniramine 0.0772%, and ketorolac 0.01%. The other, EyeFocus+, contains double the concentration of pilocarpine and the same concentrations of the other three active ingredients.¹⁶ Because compounded medications are not subject to FDA approval, the release of these drops is not dependent on a regulatory timeline.

Unlike the miotics listed above, UNR844 (Novartis Pharmaceuticals) is a lipoic acid choline ester that works by reducing disulfide bonds that form within the crystalline lens over time to increase lens elasticity. This drop is in phase 2 clinical trials.¹⁷

MORE OPTIONS, MORE SATISFIED PATIENTS

Imagine having another tool at your disposal to help your patients with their everyday frustrations from presbyopia. If and when some of the tools described here become available, not only will we be able help those with minimal distance refractive error and presbyopia to see at near, but we will also be able to combine presbyopia-correcting treatments to optimize each patient’s vision. Many of our patients could benefit from one or more of these agents in development.

For example, a patient who wears multifocal contact lenses and requires additional near vision might benefit from a miotic drop with a limited duration of action. Likewise, a patient who has had refractive surgery and would like to eliminate his or her dependence on eyeglasses. Or a patient who wears progressive lenses and works in dim illumination.

We eagerly anticipate the availability of some of these proposed options for presbyopia treatment to benefit these patients and many others.