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Experts answer clinicians’ common questions on treating patients.
With the recent approval of the first topical presbyopia-correcting drops, and several other products making their way through FDA clinical trials, many clinicians have questions about how these drops work, how they should be prescribed, and what are the risks and adverse effects.
Our practice has been involved in 4 of the clinical trials for pupil-modulating drops, and we prescribe the FDA-approved pilocarpine hydrochloride 1.25% drops (Vuity, Allergan). Here are our responses to some of the most common questions we are asked.
Every patient responds differently. At least initially, it is a good idea to counsel patients to try the drops earlier in the day or at a time when they will not need to drive in dim light. This will give them a chance to see how they function.
In our experience, the vast majority of patients experience no change in low-light image quality. For those patients who have struggled in dim light, they tend to see an improvement over time. The available clinical trial data support our anecdotal perception. The recently published GEMINI I phase 3 randomized clinical trial (NCT03804268) of 1.25% pilocarpine hydrochloride showed that under mesopic conditions, patients lost 5 or fewer letters of binocular distance acuity while gaining 3 lines of distance-corrected near visual acuity at hour 3 and day 30.1
Additionally, in a 2019 randomized study evaluating presbyopia-correcting drops containing carbachol and brimonidine tartrate, there was no dimming or loss of distance vision reported.2
These agents have been—and, in the case of pilocarpine, are still— utilized for the management of glaucoma. However, in patients with normal IOP, we would not expect pilocarpine to have anything but a transient effect because the drug can’t lower IOP below the episcleral venous pressure.3
All of the current and pipeline formulations for presbyopia correction have lower concentrations of the active compounds, which should also minimize any impact on IOP—and the study data thus far supports that expectation. In the phase 3 GEMINI I clinical trial, there was no clinically significant change in IOP at the peak near-vision efficacy point.1
Occasionally, yes. This may be the case particularly if the patient already has small pupils or gets a larger-than-expected response. Computational modeling conducted by Xu et al suggests that a 2.0- to 3.0-mm pupil, or a 30% to 40% reduction in pupil size from baseline, is likely to provide optimal near vision without compromising distance visual acuity in an emmetropic eye.4 However, the optimal pupil size may vary with changes in luminance and/or defocus. If the pupil diameter is reduced by more than 50%, patients may experience a decline in distance vision.
Such adverse effects are possible but, again, the data and our clinical experience to date suggest that that these agents have a very low adverse event profile. When adverse effects do occur, patients tend to adapt to them after just a few days.
In the GEMINI I study, there were no discontinuations, and in the pooled phase 3 studies of pilocarpine hydrochloride 1.25%, fewer than 1% of participants discontinued due to adverse effects.1
Headaches occurred in approximately 15% of patients in the pooled data set, with the majority of cases being mild and transient. The 2019 carbachol study also reported no headache or brow ache symptoms.2
There is no reason to think this will be the case. In the 2 phase 3 trials that led to the FDA approval of pilocarpine hydrochloride 1.25%, the pupils all returned to baseline after 24 hours.1 Phase 2 research with other drops so far has not shown any reduction in physiologic pupil size in participants, either.
In fact, many presbyopia-correcting drops have the opposite problem: their effect on the pupil doesn’t last long enough. Topline results from the VIVID trial for carbachol/brimonidine tartrate (Brimochol PF, Visus Therapeutics) suggest a much longer duration of up to 9 hours. But even with these longer-lasting drops, we would still expect the pupil-modulating effects to wear off each day.
Presbyopia-correcting drops will not provide complete independence from glasses or contact glasses—and that really isn’t the goal. What they do provide is flexibility.
In some cases, this might mean being able to work or go out to dinner without reading glasses. But in other cases, it might mean that drops provide multifocal contact lens wearers with a boost in their near vision, or the drops may allow someone who can’t tolerate progressive spectacles to wear single-vision glasses for distance without giving up their near vision. It’s important that clinicians prescribing presbyopia-correcting drops tell patients they still may need other forms of correction for some tasks or situations.
Given how many presbyopes there are, and the variations in their starting refractions and visual needs, we expect there will be room in the marketplace for more than 1 presbyopia-correcting drop to succeed.
Ophthalmologists, in particular, are accustomed to making permanent decisions. The replacement of a lens or the removal of corneal tissue can’t be easily undone. But with the excellent safety profile these pupil-modulating drops have demonstrated, we have the luxury of being able to advise patients to just give them a try. If the currently approved drops don’t work well for a patient, perhaps another one of the drops coming to the market in the next few years will work better.
Any patient seeking presbyopia-correcting drops should first have a comprehensive eye exam to ensure there is no evidence of contraindicated risk factors or other ocular conditions. This can help rule out patients with early lens changes, who may have a higher chance of reduced image quality, especially in low light. Practitioners may want to avoid using drops in patients with long axial length or a history of retinal tear.
Additionally, a dilated peripheral retinal exam is advisable to make sure the retina is intact and there is no lattice degeneration that might predispose the patient to retinal detachment with miotic use. In fact, one of the great advantages of this new category is that we expect it will motivate emmetropes who have never had an eye exam to finally see an eye care professional who can fully evaluate their ocular health.
This could lead to diagnosis and better management of previously undetected conditions, such as dry eye, glaucoma, or diabetic retinopathy, in addition to a prescription for drops or a recommendation for surgery to address presbyopia. It will be a great opportunity for better ocular health care for these patients.