Presbyopia Eye Drops: What the Evidence Shows (Reviewed November 2026)
By Dr Ross MacIntyre MD FRANZCO
Last reviewed: 5 November 2026
This is general information. It does not recommend any product and is not an offer to supply one. I will update this page when peer-reviewed results or an Australian regulatory decision appear.
Key Points
- In October 2026 the US FDA approved phentolamine 0.75% (Ryzumvi) drops for presbyopia in adults.
- In the larger phase 3 trial, 27.2% of treated patients reached the main endpoint on Day 8, against 11.5% on vehicle.
- Most treated patients (72.8%) did not reach that 3-line threshold, although many improved by smaller amounts.
- No presbyopia drop is currently on the Australian Register of Therapeutic Goods.
What is presbyopia and why do people look for drops?
Presbyopia is the gradual, age-related loss of the eye's ability to focus on near objects, usually noticed from the early to mid 40s. It happens because the lens stiffens and loses flexibility. Reading glasses, multifocal lenses and surgery correct it; eye drops are a newer approach that aims to reduce dependence on glasses.
Presbyopia affects virtually everyone eventually, so the appeal of a drop is obvious. The questions are how much benefit, for whom, for how long, and at what cost in side effects.
How do presbyopia drops work?
Most presbyopia drops work by changing pupil size. A smaller pupil increases depth of focus, in the same way a small camera aperture does, so near text looks sharper without changing the lens. Pilocarpine, carbachol and aceclidine constrict the pupil. Phentolamine takes a different route, blocking the signal to the muscle that widens it.
In VEGA-3, pupil diameter fell by an average of 1.17 mm in the phentolamine group and 0.21 mm on vehicle at Day 8.
What does the phentolamine evidence show?
Two phase 3 trials, VEGA-2 and VEGA-3, tested phentolamine 0.75% against vehicle in 902 randomised adults aged 40 to 64 with moderate near vision loss. In both, more treated patients reached the main endpoint on Day 8. Full results are on ClinicalTrials.gov but have not yet appeared in a peer-reviewed paper.
- Who was studied: adults aged 40 to 64 (VEGA-3 enrolled ages 45 to 64), near acuity of 20/50 to 20/100 with the usual distance correction, and distance acuity of 20/25 or better. One drop in each eye each night.
- Main endpoint: a gain of 3 or more lines (15 letters) of near acuity with under 5 letters lost at distance, 12 hours after the Day 7 dose.
- VEGA-3 (569 randomised): 27.2% against 11.5% (92 of 338 against 26 of 226). That is about 15.7 percentage points above vehicle (calculated from these figures). At 1 hour after the first dose, 20.6% against 6.1%.
- VEGA-2 (333 randomised): the FDA label reports 22.6% against 11.0% (163 against 164 patients). The registry posts a different VEGA-2 comparison, the combination arms with low-dose pilocarpine, so the label figure is the one used here.
- Smaller gains: in VEGA-3 at Day 8, 187 of 341 treated patients gained at least 10 letters, against 66 of 228 on vehicle (54.8% against 28.9%, calculated). The average gain was 10.1 against 6.1 letters, about 4 letters more than vehicle, which is less than one line.
- Durability: the average gain at Week 6 (10.5 letters) was similar to Day 8 (10.1 letters), but fewer treated patients met the responder thresholds at Week 6 than at Day 8 (3-line gain 82 against 92, and 10 or more letters 163 against 187, out of 341). The registry reports no efficacy results after Week 6 and the 48-week efficacy data have not been published.
- Limits: the trials were sponsored by Opus Genetics (formerly Ocuphire Pharma). The main endpoint was at Day 8. Results apply to the age and vision range studied.
Side effects and safety
The label's figures pool 534 treated patients: conjunctival hyperaemia (redness) 21% and instillation site irritation 16%. In VEGA-3 specifically, over up to 48 weeks: redness 27.9% against 1.8% on vehicle; instillation site irritation 16.1% against 1.3%; altered taste 5.9% against 0.4%; headache 3.5% against 1.3%. Serious adverse events were reported in 4 of 341 treated patients (1.2%) and 3 of 228 on vehicle (1.3%). One treated patient had a retinal vein occlusion. The registry does not say whether any serious event was related to the drug. Of treated patients, 31.7% did not complete the 48-week study, against 14.5% on vehicle. The registry does not give reasons, so the cause is unknown.
The label advises against use with active ocular inflammation such as iritis. Contact lenses must be removed before dosing and can be reinserted 10 minutes after dosing. The label contains no statement about driving or night vision.
How does phentolamine compare with other presbyopia drops?
Direct comparison is not possible. Other drops, including pilocarpine (Qlosi), aceclidine (Vizz) and carbachol with brimonidine (Yuvezzi), were tested in separate trials with different endpoints, time points and lighting. No trial comparing two of these products directly was found in a PubMed search on 5 November 2026, so differences in reported percentages do not show which drop works better.
Small trials have compared a combination with its own components, such as carbachol plus brimonidine against each alone, which does not show which product works better.
| Drop | Active ingredient | How it works | US status |
|---|---|---|---|
| Qlosi | Pilocarpine 0.4% | Constricts the pupil | FDA approved October 2023 |
| Vizz | Aceclidine 1.44% | Constricts the pupil with little effect on the focusing muscle | FDA approved July 2025 |
| Yuvezzi | Carbachol 2.75% with brimonidine 0.1% | Constricts the pupil | FDA approved January 2026 |
| Ryzumvi | Phentolamine 0.75% | Blocks the signal to the muscle that widens the pupil | FDA approved for presbyopia October 2026 |
| Vuity | Pilocarpine 1.25% | Constricts the pupil | Approved 2021, listed as discontinued on Drugs@FDA |
The Vuity label, as it stood when the product was marketed, advised caution in night driving and an examination of the retina in all patients because of a risk of retinal detachment (Drugs@FDA record for Vuity).
Who may not be suitable for presbyopia drops?
Suitability depends on age, glasses prescription and eye health. In the phentolamine trials, participants were 40 to 64 with moderate near vision loss. The label advises against use in active ocular inflammation such as iritis. I would be cautious in higher uncorrected long-sightedness, advanced presbyopia, and meaningful dry eye or surface disease.
Are presbyopia drops available in Australia?
As of 5 November 2026, no presbyopia eye drop appears on the Australian Register of Therapeutic Goods. The TGA lists one application under evaluation, Aspen's Qlosi (pilocarpine 0.4%), accepted in June 2026. Acceptance for evaluation is not approval. No application for phentolamine for presbyopia appears on the TGA list.
The only registered pilocarpine eye drops are products registered for glaucoma and related uses (Isopto Carpine and Minims Pilocarpine). They are not registered for presbyopia, and any use for presbyopia would be off-label and a decision for a treating doctor. US approval does not mean availability in Australia.
What are the other options for presbyopia?
Established options include reading glasses, bifocal or progressive lenses, multifocal contact lenses and monovision. Surgical options include laser monovision and lens replacement with multifocal or extended depth of focus lenses, which suit some patients but carry their own trade-offs. Which is appropriate depends on your eyes, your lifestyle and an examination.
Our guides to refractive lens exchange and intraocular lens options explain the lens-based choices in more detail.
Sources
- Ryzumvi (phentolamine ophthalmic solution) prescribing information, DailyMed
- VEGA-3, NCT06542497, ClinicalTrials.gov
- VEGA-2, NCT05646719, ClinicalTrials.gov
- Australian Register of Therapeutic Goods (ARTG), TGA
- Prescription medicines under evaluation, TGA
- PubMed, searched 5 November 2026 for trials comparing phentolamine, pilocarpine, aceclidine, carbachol and brimonidine in presbyopia
- US prescribing information on DailyMed: Qlosi, Vizz and Yuvezzi
- Vuity, NDA 214028, Drugs@FDA