The first drop for presbyopia, Vuity (pilocarpine hydrochloride, Allergan), has recently gained FDA approval and has received much attention. It provides a pharmaceutical option beyond spectacles, contact lenses and surgery. The new drug is now readily available and easy to administer with fast onset and sufficient duration for most (about six hours). Even though this product has only been used for just a few months, reports have been positive. As with any newly approved product, time will tell just how well it will be embraced by patients and providers. How might these products help contact lens wearers? Is there a place for those with early presbyopic symptoms? How about patients past their mid-40s who require some add power to see well at both distance and near? What major effect(s) do these products have on lens optics, since they work by making the pupil smaller? Only time and experience will help answer these questions.

Where We’re At
Remember that lens wear results in a greater stimulus to accommodate than spectacles, which then requires an earlier need for help at near. I think it’s safe to assume there might be some benefit in using drops for presbyopia in early presbyopic lens wearers, even prior to or in lieu of relying on one-eye undercorrection or low-add powered lenses. Any synergy when using multifocal contact lenses with presbyopic drops might be possible with low-add powered contact lenses so not to affect distance acuity. Higher add powers (mid-high) require lens designs that add negative spherical aberrations (distanced defocus) to extend the depth of focus. Unfortunately, this increases the blur circle, thereby affecting distance acuity, and smaller pupils reduce retinal illumination, lowering contrast sensitivity. In addition to some variations in pupil size effects in using these products, there may be somewhat different responses depending on specific multifocal/bifocal designs (simultaneous vs. alternating) worn. Some designs are pupil dependent while others have less overall effect on optics based on pupil size. The drawbacks in using these drops with contact lenses are its durability and minimal amplitude effect. The newly approved Vuity provides about 1.25D to 1.50D of amplitude for a relatively short period of time. Some clinicians are asking patients to use the drops more than once daily (off-label).

Other Choices
The pipeline is replete with options to help presbyopes. Many manufacturers are using a cholinergic muscarinic agonist such as pilocarpine. I am aware of at least six other compounds in clinical trials that produce miosis and should aid in managing presbyopia. Most are in the Phase III FDA pre-market approval process. Lenz Therapeutics is studying the use of aceclidine (miotic) and Visus Therapeutics is using a combination carbachol/brimonidine for a possible dual/synergistic action. Novartis has a unique product that uses a lipoic acid/choline ester compound and may be effective in enhancing accommodation along with affecting depth of focus. It reduces dihydrolipoic acid within the lens fibers, which causes hydrolysis of the disulfide protein bonds and restores lens elasticity. I do have some reservations in patients who might use pilocarpine for years prior to cataract surgery and may not get adequate dilation for their cataract removal. Warn patients, on initial use, about a “dimming effect” and that they should avoid using this drop in poor lighting conditions such as driving at night. Of course, there have been exceedingly rare adverse events such as iris cysts, angle widening resulting in angle closure (often used to treat angle closure glaucoma but paradoxical in spherophakia patients), accommodative spasm and retinal detachment in myopes (not often reported with low concentrations). Careful instruction for patients to discontinue miotics prior to dilation will be required.

In addition, Orasis Pharmaceuticals recently reported that their Phase 3 NEAR-1 and NEAR-2 clinical trials, which evaluated the efficacy and safety of CSF-1, its novel eye drop candidate, met their primary and key secondary endpoints. These results were achieved with a minimum effective dose of pilocarpine hydrochloride at 0.4%, which is less than one-third the concentration of the commercially available treatment, Orasis said. Details of these trials will serve as the basis for company’s New Drug Application submission to the U.S. Food and Drug Administration (FDA) in the second half of 2022.

We’ll see if these new options for presbyopia are game-changers. Patients will know early on whether Vuity makes sense for them. Overall, the response has been favorable for those who are properly screened and have had an adequate education on how to best use the drop.

A version of this article was first published in Review of Cornea & Contact Lenses, March/April 2022. It is reproduced here with permission from the publisher.