Introduction
As we know, presbyopia is an age-related condition that leads to difficulty focusing on near objects.1 This gradual loss of accommodation begins in childhood.2 Corrective options for presbyopia have historically included spectacles, contact lenses, refractive surgery, and, more recently, pharmaceutical drops.1 Research indicates that 10% of patients with presbyopia would be willing to sacrifice 5% of their remaining lifetime, and about 6% would trade 10% of their life to eliminate the condition.3
This effect on quality of life raises the question: What treatment options can we offer our presbyopia patients to ensure flexibility?
Overview of Presbyopia
Presbyopia occurs due to a combination of ocular lens stiffening, ciliary muscle and zonular aging, and biomechanical changes in the parts involved in the accommodation process.2 Presbyopia significantly impacts the quality of life for many, as it can affect work productivity3 and other near tasks.1
Many risk factors are associated with the development of presbyopia (Table 1), the most significant of which we are all familiar with is aging. Refractive errors like hyperopia (4-7X) and myopia (2X) increase the risk of earlier onset presbyopia compared to emmetropia.3 It’s important to note that myopic contact lens wearers may report symptoms earlier due to the increased accommodative demand they experience while wearing contact lenses.4
Other risk factors include geographic location, as individuals in countries closer to the equator tend to have an earlier age of onset, and women are more likely to develop it sooner.1 Certain medical conditions, such as cardiovascular disease, diabetes, and multiple sclerosis, and medications like antihistamines and antidepressants may also contribute to an earlier age of onset.3
Table 1. Presbyopia Risk Factors3,4
Prevalence
Approximately 85% of individuals over the age of 40 will develop presbyopia, and the prevalence increases with age. By 2030, around 2.1 billion people worldwide will be affected by it.1 In North America, 80% of the presbyopic population is between 45 and 55, with 16% lacking adequate vision correction.5 In the United States, based on estimates that assume everyone over 45 has some degree of presbyopia, about 139 million people are affected.6
Diagnosis
A comprehensive examination is essential to diagnosing presbyopia and identifying suitable treatment options.4 Patients report common symptoms related to reading, including a need for increased light, diplopia, epiphora, headache, fatigue, and asthenopia.1
Mild presbyopes may employ coping strategies to hold off treatment, including:
- Holding objects further away
- Using brighter lighting (especially in dim lighting)
- Increasing font sizes
- Wearing OTC reading glasses
- Myopes taking off distance correcting glasses to read.4
After evaluating their symptoms and coping strategies, determine the patient’s refractive status, best-corrected visual acuity (BCVA), binocular status, and the health of the anterior and posterior segments of the eyes. Assessing the clarity of the crystalline lens can help rule out cataracts as the primary cause of reduced visual acuity. Furthermore, examining peripheral retinal health is essential due to the increased risk of retinal detachment, which may be associated with certain presbyopia-correcting drops.2
The Need to Proactively Address Emerging Presbyopes
In my experience, early education is very important for emerging presbyopes. It’s important to discuss symptoms, stress the importance of routine comprehensive exams, and discuss available treatment options. Additionally, take the time to understand your patient's visual needs, particularly about their lifestyles and hobbies.
Treatment Options for Presbyopia
There are several treatment options for correcting presbyopia, and understanding the advantages and disadvantages is vital to matching the patient to the right one (Figure 1).7
Spectacles
Some patients might be satisfied with spectacle lenses because they offer a simple, easy, and practical solution. However, there are some considerations eyecare providers should consider when prescribing spectacles, the most important being an increased fall risk.4 Many people consider glasses inconvenient because they often forget to wear them and may feel limited in the activities they can participate in. Some individuals report discomfort from the physical pressure of wearing glasses and experience eye strain from not addressing their vision needs. Additionally, there is a psychosocial aspect, as wearing glasses can make some feel and look older.8
Contact Lenses
Contact lenses are another option for presbyopia correction, with a few different approaches. A practitioner can prescribe monovision and multifocal contact lenses, but these options are not without issues.1 Monovision often results in reduced contrast sensitivity and stereopsis, which can limit night driving. Reusable soft lenses also carry an increased risk of contact lens complications compared to daily disposable soft lenses.4
In the United States, less than half of patients with presbyopia who use contact lenses are offered multifocal or monovision options. Among those who received these options, only 50% continued to use them after six months.9
Surgical
Some patients may seek more permanent presbyopia treatment options because of the increased use of digital devices and the fact that more people are working past retirement age. Options include refractive lens exchange, corneal inlays, scleral correction, monovision vision and multifocal LASIK, and monovision PRK.1 These options have drawbacks, including impacted distance vision, dysphotopsia, and complications associated with surgery.4
Pharmaceutical
Pharmaceuticals provide a non-invasive and reversible approach to treating presbyopia.2 A study by Stokes et al. (2022) found that ¾ of participants ranked eye drops as their first or second preferred option. Study participants ranked them preferable because they are discreet and convenient compared to glasses, less invasive than contact lenses and surgery, and less expensive than surgery.8
The pharmaceutical treatment options for presbyopia utilize pupil modulation. Pupil modulation increases the depth of field through parasympathetic-mediated miosis.1 Research was conducted on a pharmaceutical drop that softened the lens to relieve the symptoms associated with presbyopia temporarily; however, these investigations have been suspended.2
Current FDA-approved formulations for presbyopia correction include Pilocarpine HCL 0.4% (QLOSI, CSF-1; Orasis Pharmaceuticals) and Pilocarpine HCL 1.25% (Vuity; AGN-190584; Allergan, Inc., an AbbVie company).2
Indication
Qlosi (pilocarpine ophthalmic solution) 0.4% is a prescription eye drop used to treat age-related blurry near vision (presbyopia) in adults.
QLOSI
QLOSI [cloh-see] (Orasis Pharmaceuticals) is an FDA-approved 0.4% pilocarpine HCL ophthalmic solution with less than one-third the concentration of Vuity. Pilocarpine is a direct-acting full- and partial-cholinergic agonist of the five muscarinic receptor subtypes, particularly M3.2 QLOSI contracts the iris sphincter muscle, constricting the pupil to enhance the depth of focus and improve near visual acuity while maintaining some pupillary response to light.10 It achieved all primary, secondary, and exploratory endpoints in the NEAR-1 (NCT04599933) and NEAR-2 (NCT04599972) clinical trials. Side effects included headaches, instillation site pain, blurred vision, and conjunctival hyperemia.11
Vuity
Vuity (Allergan, Inc., an AbbVie company) was the first FDA-approved pharmaceutical drop. GEMINI 1 (NCT03804268) and 2 (NCT03857542) trials achieved their primary endpoint. Trial subjects achieved an increase of ≥3 lines while maintaining distance vision with no loss of ≥5 letters. The effects of Vuity were noted within 15 minutes and lasted for up to 6 hours. The most common side effects were headaches, conjunctival hyperemia, blurred vision, and eye pain. VIRGO investigated the effect of twice-daily dosing and has been approved.2
The following pharmaceutical correction option is currently in the clinical trial process.2
Nyxol
Nyxol (Opus Genetics), 0.75% phentolamine ophthalmic solution, is a non-selective alpha-adrenergic blocker primarily used for its vasodilatory effects on blood vessels. It blocks both alpha-1 and alpha-2 receptors, resulting in the relaxation of smooth muscles, which in turn causes vasodilation and pupil constriction. Prior clinical trials investigated a combined solution of phentolamine and pilocarpine2, but the ongoing VEGA-3 Phase 3 trial (NCT06542497) is investigating only the 0.75% phentolamine ophthalmic solution. Previous studies suggest it has a good safety profile.12
The following pharmaceutical correction options have been submitted for New Drug Application.13,14
Brimochol PF
Brimochol PF (Tenpoint Therapeutics) combines 2.75% carbachol + 0.1% brimonidine tartate.
Carbachol is a parasympathomimetic that functions as a full agonist at both muscarinic and nicotinic receptors, leading to the significant release of acetylcholine from parasympathetic nerve endings. It produces a prolonged miotic effect, resulting in pupil constriction. Brimonidine is an adrenergic agonist with a strong affinity for alpha-2 receptors. It interacts with presynaptic nerve endings linked to the dilator muscle, potentially reducing miotic side effects and decreasing the dilator muscle's activity.2
BRIO-I demonstrated a gain of 15 or more ETDRS letters in best near visual acuity without a loss of 5 or more letters in distance vision across all time points during a 6-hour period. Side effects included eye irritation and headaches.2
BRIO-II was a 12-month study that achieved its primary endpoints, showing a significant improvement of three lines or more in binocular uncorrected near visual acuity (BUNVA) over an 8-hour period, with no decline in binocular uncorrected distance visual acuity (BUDVA). The study was well tolerated, with no serious treatment-related adverse events reported during over 70,000 monitored treatment days. Tenpoint Therapeutics has submitted a New Drug Application for Bimochol PF.13
LNZ100
The LNZ100 (Lenz Therapeutics) phase 2 INSIGHT trial investigated LNZ 100 (1.75% aceclidine) and LNZ 101 (1.75% aceclidine and brimonidine). The phase 2 Insight trials showed a ≥ 3-line improvement in VA without a corresponding loss of ≥1-line in DVA within the first-hour post-treatment LNZ 100 and LNZ 101. Aceclidine is a selective cholinergic miotic agent that binds to acetylcholine receptors in the autonomic nervous system. It primarily targets the pupil's sphincter muscles while having minimal effects on the ciliary muscles.2
The CLARITY 1 (NCT05656027) and 2 (NCT05728944) trials investigated LNZ 100 and LNZ 101. LNZ 100 had a rapid onset of action with significant improvement in near vision lasting up to 10 hours and ≥2-line improvement in near vision after 1 hour. Side effects include eye irritation, visual impairment, and headaches.2 LNZ 100 has been submitted for approval for a new drug application, and the CLARITY 3 trial (NCT05753189) has been completed.14
Figure 1. Presbyopia treatment options7
A Closer Look at QLOSI and Its EyeQ Formulation™
QLOSI is an eye drop designed to treat presbyopia in adults. Its unique EyeQ Formulation combines four key features (Figure 2). One of the key features is 0.4% pilocarpine HCL, which allows for this ingredient's lowest effective concentration. Another feature is the near-neutral pH of the solution, which enhances bioavailability, making it effective at a minimal dose. Additionally, dual lubricating agents and a preservative-free solution support the ocular surface health.15
Figure 2. Qlosi™ EyeQ Formulation™
Due to its dosing flexibility, it allows for clear near vision on demand. Patients can use one drop of Qlosi in each eye. This can be repeated within 2-3 hours after the first instillation and lasts for up to 8 hours.15
Efficacy
Qlosi achieved all primary, secondary, and exploratory endpoints in the NEAR-1 (
NCT04599933) and NEAR-2 (
NCT04599972) clinical trials. These identically designed Phase III multicenter, randomized, double-masked, vehicle-controlled, parallel-group studies were conducted at 35 US sites with 613 participants. These two-week studies with twice-daily administration showed a favorable safety and tolerability profile.
11 The pooled results are reported here.
Primary Endpoint
40.1% of participants had ≥3-line gain in mesopic, distance-corrected near visual acuity (DCNVA), and no loss of 1-line or more in distance visual acuity on DAY 8 at 1 hour in the monocular study eye (Figure 3).11
Key Secondary Endpoints
NEAR-1 and NEAR-2 successfully met their key secondary endpoints in the monocular study eye. Specifically, the proportion of participants who achieved a≥ 2-line improvement in Distance Corrected Near Visual Acuity (DCNVA) without losing one line or more in distance visual acuity on Day 8 was as follows: 39.8% at 2 hours post-dose 1, 49.5% at 1 hour post-dose 2, and 42.4% at 2 hours post-dose 2. In comparison, the corresponding percentages for the vehicle group were 18.8%, 16.1%, and 17.4%, respectively (Figure 3).11
Figure 3. Primary and Key Secondary Endpoints from NEAR-1 and NEAR-211
Exploratory Endpoints
For presbyopic patients, a 10-letter gain in DCNVA observed on days 8 and 15 represents a clinically meaningful improvement in visual care and functional vision.11 Approximately 80% of patients taking QLOSI achieved 20/40 near vision or better after either the first or second dose on Day 15 when tested with binocular vision.16 In my opinion, this binocular summation plays a significant role in the improved outcomes for distance-corrected near visual acuity (DCNVA), as it reflects how patients typically use both eyes for daily activities (Figure 4).
Figure 4. Monocular vs. Binocular vision after 2 doses on Day 1516
QLOSI achieved an optimum pupil size of 2-3mm within 20 minutes.11 Research indicates that this pupil size enhances the depth of focus without introducing the risk of diffraction and does not affect mean distance vision across various lighting conditions.17 Pupil reduction was maintained throughout the day, from 20 minutes to up to 8 hours.11 Additionally, the number of 2-line and 3-line responders increased from day 1 to day 15, without a corresponding change in the average pupil diameter, suggesting that neuroadaptation may play a role in vision improvement. Figure 5 shows the 3-Line improvement on Days 1, 8, and 15 compared to pupil size.11
Figure 5. Qlosi Demonstrated Consistent Improvement In DCNVA Over Time With Consistent Pupil Reduction11
Safety
QLOSI has an acceptable safety profile, as most adverse effects were mild. The most common adverse events with QLOSI were headaches, instillation site pain, blurred vision, and conjunctival hyperemia, as shown in Table 2. Instillation site pain lasted 10 seconds to 2 minutes, but it was scored 2/10 for comfort, meaning most users found it tolerable. The drop comfort scale reported by subjects ranged from 0, indicating very comfortable, to 10, indicating very uncomfortable.11
Table 2. The most common Treatment-Related Adverse Events from NEAR-1 and NEAR-211
Implementing QLOSI in clinical practice
Patient education and selection are critical in determining the appropriate candidates for Qlosi. The ideal patient is someone who is starting to experience presbyopia and is an emmetrope, mild myope, or mild hyperope. This person desires to be free from glasses and may not have adjusted well to monovision or multifocal contact lenses. Additionally, these patients might be motivated by their lifestyle to take a break from reading glasses, whether for special occasions or all-day use.
Concerns about cost may arise when considering Qlosi. However, the lack of prior insurance authorization requirements simplifies prescribing and ensures prescriptions are issued without delay. It also means all patients pay the same price. FSA and HSA funds can be used to maximize affordability, offering potential tax savings. For further convenience, Qlosi is shipped directly to patients' homes, and a subscription service is available for seamless refills.
Other candidates to consider who were not included in the NEAR-1 and NEAR-2 studies are single-vision contact lens wearers and patients with a history of cataract surgery or refractive surgery distance correction. Like multi-focal contact lenses or progressives, always discuss how neuroadaptation improves over time to reduce patient dropout.
For patients who plan to wear contact lenses with QLOSI, instruct them to wait 10 minutes after instilling the drop before wearing their contact lenses. For those who use other ophthalmic medications, wait 5 minutes before administering them.10 Patients should also be educated about being cautious with night driving.
Staff education and involvement are crucial in addressing treatment options for presbyopia. Hold meetings to educate your team about these options. It is important for all staff members—from the front desk to opticians—to be knowledgeable about the treatments available. Remember, some staff members will spend more time with patients than you will, making it a valuable opportunity for them to discuss treatment plans. This way, patients can ask you about their options during their time with you.
Conclusion
The treatment options for patients with presbyopia are expanding, providing practitioners with a variety of solutions tailored to different lifestyles. From glasses to pharmaceutical drops, the possibilities are numerous and diverse. Excellent patient communication is essential for addressing concerns and offering suitable treatment options.
QLOSI is the latest FDA-approved medication for treating presbyopia. It is effective for up to eight hours and can be taken once or twice a day. The unique EyeQ formulation contains 0.4% pilocarpine, is preservative-free, has a near-neutral pH, and includes lubricating agents to help support ocular health.
QLOSI was launched on 4/7/2025 and is available only through BlinkRx and Medvantyx specialty pharmacies.
