FDA Approves Eye Drops for Presbyopia

Laird Harrison

November 01, 2021

Updated November 3, 2021 // Editor's Note: This story has been updated with additional comments from Dr Christopher Starr and Eyenovia COO Michael Rowe.

The US Food and Drug Administration for the first time has approved an eye drop to treat presbyopia, also known as age-related blurry near vision, in adults.

Pilocarpine HCl ophthalmic solution 1.25% (Vuity) contracts the pupil size in a pinhole-camera effect. It could allow people with good distance vision to forego their reading glasses in many situations and might expand interest in refractive surgery such as LASIK.

"This affects almost half of the U.S. population,” said George O. Waring IV, MD, in an interview with Medscape Medical News. Waring is the medical director of the Waring Vision Institute in South Carolina, and led the phase 3 clinical trials. "That's 120 million adults in the US. It's rare that we have an opportunity to help that many people with a new medical offering, and that's why we consider this a landmark event.”

The drops must be administered daily, require at least 15 minutes to take effect, and improve near vision up to 6 hours and intermediate vision for up to 10 hours.

Ophthalmologists have long known that miotics can improve near vision by contracting the iris sphincter, which reduces the pupil size and creates the pinhole-camera effect. Some drugs, including pilocarpine, may also increase accommodation through mild contraction of the ciliary muscle.

But, combined with preservatives, these eyedrops often cause side effects, including stinging, headaches, brow aches, and loss of mesopic vision. In rare instances, pilocarpine has been associated with retinal detachment. Partly for these reasons, pilocarpine is no longer commonly used to treat glaucoma. AbbVie credits its "proprietary pHast technology" for allowing pilocarpine to adjust to the pH of the tear film, reducing the stinging sensation and perhaps increasing efficacy.

According to the label, the drops are preserved with benzalkonium chloride 0.0075%. The inactive ingredients include boric acid, sodium citrate dihydrate, sodium chloride, purified water, and "may also include hydrochloric acid and/or sodium hydroxide for pH adjustment to between 3.5 and 5.5, if necessary."

For the two phase 3 trials, the investigators recruited a total of 750 people with presbyopia and randomly assigned them to receive either pilocarpine or the vehicle as a placebo.

The patients took the drops in both eyes once a day for 30 days. The researchers tested the participants at day 30, hour 3 to see how many had gained three ETDRS lines or more in mesopic, high-contrast, binocular distance-corrected near visual acuity without losing more than 5 lines of distance vision, a standard of success set by the FDA.

In both trials, more people in the pilocarpine group than in the placebo group met this standard at 3 hours, and the difference was statistically significant, the researchers say.

In Gemini 2, the drug's effects peaked after 1 hour, when 37.3% of patients in the pilocarpine group achieved this standard, compared to 12.1% of those given only the vehicle as a placebo, a difference that was statistically significant (difference 25.2 percentage points; confidence interval 17.0 - 33.4).

The proportion achieving this standard declined steadily after the first hour, reaching 16.3% in the pilocarpine group and 9.9% in the placebo group at hour 6.

The researchers also indicated that a significant proportion of patients reported improvement in vision-related reading ability on questionnaires. The patients also indicated that presbyopia as well as the use of "coping behaviors" to manage presbyopia had less of an impact on daily life.

No serious adverse events were associated with the use of pilocarpine. As many as 15% of the subjects who took pilocarpine reported headaches, Waring said. But these were mild and transient, and 7% of those in the placebo group also reported headaches. Conjunctival hyperemia, blurred vision, and eye pain were also reported.

Waring said since the drug won't last all day, the company is studying what happens if people take a second dose in the same day. The drops could be a first-line treatment for presbyopia in many patients, he said.

"Glasses, contact lenses, and surgery are traditional treatments, but, for various reasons, do not work well for every patient," said Christopher Starr, MD, clinical spokesperson for the American Academy of Ophthalmology, in an email. "Having a novel treatment option in the form of a presbyopia eye drop is a welcome addition to our armamentarium against this universal, age-related near-vision condition that affects essentially everyone over the age of 40."

Multiple other companies are working on drops that would work by a similar effect, including at least one compounding pharmacy whose product might be sold without needing FDA approval. Some, like AbbVie's pilocarpine, may be administered in both eyes, whereas others are administered in only one eye to preserve vision in dim light.

Each comes with its pros and cons, said Michael Rowe, chief operating office of Eyenovia, whose 2% pilocarpine solution, MicroLine, has completed one phase 3 trial and started another.

By putting 1.25% pilocarpine in a buffering vehicle, AbbVie was able to reduce the side effects associated with the compound while getting FDA approval more quickly than its rivals, he said.

Other companies are testing combination drugs that might be safer or more effective, but the FDA requires proof that each of the drugs is effective on its own as well as in combination, Rowe said.

MicroLine uses a patented applicator to spray 2% pilocarpine solution. Because the doses are much smaller, side effects are reduced, he said.

But none of the miotics can quite take the place of reading glasses, said Rowe. "There's just so much more you can actually do with a piece of glass then you can with relying on the body and the pinhole effect of constricting the pupil." Reading your cell phone will probably be possible. Grading term papers? Not so much.

Instead, the drugs can serve as an alternative to be used in a social situation or very active situation where reading glasses are undesirable. "The way we look at it, it's almost like getting a second pair of reading glasses. But the second pair is your invisible pair."

In addition, Rowe said, many people with presbyopia won't be able to benefit from the drugs because they still require some ability to accommodate. Most people lose that altogether after about age 55.

Waring and Starr both report financial relationships to AbbVie. Rowe is an employee of Eyenovia.

Laird Harrison writes about science, health, and culture. His work has appeared in national magazines, in newspapers, on public radio, and on websites. He is at work on a novel about alternate realities in physics. Harrison teaches writing at the Writers Grotto. Visit him at lairdharrison.com or follow him on Twitter @LairdH

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