Rachael Wruble, OD, of Belmont Eye in Belmont, North Carolina, and Mahsa Masoudi, OD, FAAO, of Marietta Eye Clinic in Marietta, Georgia, sat down to compare notes on how their approach to presbyopia drops has evolved.
Dr. Wruble was an early adopter and speaker for the first pilocarpine drop to reach the market; Dr. Masoudi, whose practice skews toward glaucoma, was not—she found the earlier concentration hard to justify for patients already managing polypharmacy and compromised ocular surfaces. Their conversation traces how that early skepticism gave way to routine prescribing, and what changed their minds along the way.
Early doubts following first-generation presbyopia therapies
Dr. Masoudi's early hesitation centered on a real pharmacologic tradeoff: pilocarpine binds all five muscarinic receptor subtypes (M1 through M5), but only the M3 receptor drives the pupillary constriction that produces presbyopia's therapeutic pinhole effect.1
At higher concentrations, more drug reaches the M5 receptors concentrated in the ciliary body and retina—tissue where stimulation doesn't improve near vision but does raise the risk of side effects like brow ache, dim vision, and myopic shift.1
A drop formulated at roughly a third or less of earlier concentrations reduces the amount of drug reaching those off-target M5 sites while preserving enough M3 activity at the iris sphincter to constrict the pupil.1 That receptor math is why concentration, not just the presence of pilocarpine, determines a patient's experience.
For Dr. Masoudi's glaucoma-heavy patient population—many already on multiple preserved drops with compromised corneal surfaces—that tradeoff, combined with a preservative-free formulation in addition to the lower concentration, was what moved her from skeptic to prescriber.
How newer presbyopia drops differ
Both doctors pointed to dosing flexibility as a practical differentiator, and the pooled phase 3 data behind QLOSI (pilocarpine HCl 0.4%) backs that up. Across the NEAR-1 and NEAR-2 trials, QLOSI demonstrated meaningful improvement in near vision at multiple assessment points; the proportion of patients achieving 20/40 or better near vision rose from 74% on day 1 to 89% by day 8.2
Dr. Wruble pointed out that the labeled onset begins at approximately 20 minutes, and a second dose administered 2 to 3 hours after the first may extend the effect for up to 8 hours.
“We have emerging data supporting the physiological response, and we can really educate the patients.”
That efficacy window lines up with the dosing flexibility both doctors described. Onset occurs within 20 minutes of administration, and a second dose—if a patient needs it—can be taken 2 to 3 hours after the first, extending coverage to as long as 8 hours.3
In the pooled trials, QLOSI was well tolerated, with no single adverse event occurring in more than 10% of patients; the most common were headache (6.8%) and instillation-site pain (5.8%).2 That tolerability profile is consistent with what Dr. Wruble and Dr. Masoudi described: most patients settling into once-daily use after an initial adjustment period.
Debunking common misconceptions
Dr. Wruble referenced a Bascom Palmer Eye Institute study comparing pilocarpine 0.4%, pilocarpine 2%, and balanced salt solution—and the data support the pupil-selectivity claim she described. In a head-to-head study conducted at Bascom Palmer, imaging showed pilocarpine 0.4% produced pupil constriction while ciliary muscle accommodative response was not significantly different from the balanced salt solution control.4
The authors note this was a small mechanistic study involving 10 subjects. It compared pilocarpine 0.4% with pilocarpine 2% and balanced salt solution—not directly with pilocarpine 1.25%—and was not designed to establish comparative rates of retinal adverse events.
The study established that the lower-concentration formulation achieved the pinhole effect responsible for improved near vision without meaningfully engaging the ciliary muscle—the mechanism both doctors linked to unwanted side effects like brow ache and blur at distance.
That distinction matters for how clinicians frame the drop category to patients and colleagues. "It's all just pilocarpine" treats concentration as a footnote; the ciliary muscle data suggest it's closer to the whole story.
“The problem is a lot of my patients are dilated before I see them, being a more medical heavy practice with trained paraoptometric staff to do the initial workups, so the conversation is retroactive.”
It also reframes patient selection: since pupil size and accommodative response—not just presbyopia severity—influence how a given patient responds, baseline pupil measurement during dilation becomes a data point worth documenting before prescribing rather than an incidental exam finding. Natural baseline pupil size, measured before dilation, may be a useful data point when evaluating and following patients.
Patient conversations are easier than expected
Dr. Wruble's math—a drop conversation added to an exam in under 60 seconds— scales against a genuinely large patient population. Presbyopia affected an estimated 1.8 billion people globally in 2015, roughly a quarter of the world's population, and that number is projected to grow to 2.1 billion by 2030 as the population ages.5
Nearly every optometric exam room will eventually include a presbyopic patient, which is part of why both doctors described defaulting to mentioning drops as one of three standard options—glasses, contacts, or drops—rather than waiting for patients to raise the topic themselves.
The reluctance some colleagues describe ("I don't have time to talk about it") doesn't hold up against that scale of need, or against the doctors' shared experience that most patients decide quickly once they understand the tradeoffs.
Setting expectations up front—possible mild headache or instillation discomfort, appropriate dosing based on the patient’s needs, and follow-up to reassess—appears to do most of the work of the conversation before the patient ever leaves the chair.
In closing
Dr. Wruble and Dr. Masoudi's paths to prescribing confidence looked different—one built on early, hands-on experience with the category's first generation, the other on staying out of it until the formulation made sense for her patient population.
However, they converged on the same conclusion: concentration and formulation, not the presence of pilocarpine alone, determine which patients benefit and how the conversation should go.
For ODs who tried an earlier-generation drop and moved on, or who have avoided the category altogether, both doctors' experience suggests the conversation may be shorter, and the range of appropriate patients broader, than some clinicians initially assume—provided that patient selection, retinal examination, and counseling remain central.
