Inclusion Criteria

• ≥40 and ≤64 years of age
• BCDVA of 0.0 LogMAR (20/20 Snellen equivalent) or better in each eye under photopic conditions
• DCNVA of 0.4 LogMAR (20/50 Snellen equivalent) or worse under photopic conditions in each eye and binocularly
• Subjects who depend on reading glasses or bifocals in which their binocular best-corrected near VA is 0.1 LogMAR (20/25 Snellen equivalent) or better

Exclusion Criteria

Ophthalmic:^*

• Use of any topical prescription or over-the-counter (OTC) ophthalmic medications within 7 days of screening until study completion
• Use of any OTC artificial tears (preserved or unpreserved) at least once per day within 7 days of screening until study completion
• Current use of any topical ophthalmic therapy for dry eye
• Tear break-up time of <5 seconds or corneal fluorescein staining (CFS) Grade ≥2 in the inferior zone or ≥1 in the central zone using the National Eye Institute scale
• Clinically significant ocular disease that might interfere with the study as deemed by the Investigator
• Recent or current evidence of ocular infection or inflammation
• Any history of herpes simplex or herpes zoster keratitis
• History of diabetic retinopathy or diabetic macular edema
• Known allergy, hypersensitivity, or contraindication to any component of the phentolamine, pilocarpine, or vehicle (placebo) formulations
• History of cauterization of the punctum or punctal plug (silicone or collagen) insertion or removal
• Ocular trauma, ocular surgery, ocular laser treatment within 6 months prior to screening
• Use of multifocal intraocular lenses
• History of any traumatic (surgical or nonsurgical) or nontraumatic condition affecting the pupil or iris
• Unwilling or unable to discontinue contact lens use
• Conjunctival hyperemia ≥Grade 2 on the Cornea and Contact Lens Research Unit (CCLRU) 4-point scale

Exclusion Criteria

Systemic:

• Known hypersensitivity or contraindication to alpha- and/or beta-adrenoceptor antagonists or any systemic cholinergic parasympathomimetic agents
• Clinically significant systemic disease that might interfere with the study as deemed by the Investigator
• Participation in any investigational study within 30 days prior to screening
• Females of childbearing potential who are pregnant, nursing, planning a pregnancy, or not using a medically acceptable form of birth control
• Resting HR outside the range of ≤50 to ≥110 bpm
• Hypertension with resting DBP >105 mmHg or SBP >160 mmHg

Primary Endpoint

• Percentage of subjects with ≥15 letters of improvement in photopic binocular DCNVA from baseline to visit 2 at 1 hour with POS + LDP compared to placebo alone

Key Secondary Endpoints

• Percentage of subjects with improvement of ≥15 letters in DCNVA (photopic) at 1 hour and with <5 letters of loss in photopic binocular BCDVA from baseline to visit 2 at 30 min, 1 hour, 2 hours, 3 hours, 4 hours, and 6 hours comparing POS + LDP to POS alone, placebo + LDP, and placebo alone
• Percentage of subjects with improvement of ≥5, ≥10, and ≥15 letters in DCNVA (photopic) from baseline to visit 2 at 30 min, 1 hour, 2 hours, 3 hours, 4 hours, and 6 hours comparing POS + LDP to POS alone, placebo + LDP, and placebo alone
• Change in DCNVA (photopic) from baseline to visit 2 at 30 min, 1 hour, 2 hours, 3 hours, 4 hours, and 6 hours comparing POS + LDP to POS alone, placebo + LDP, and placebo alone
• Percentage of subjects with improvement in DCNVA (mesopic) from baseline to visit 2 at 2 hours, 4 hours, and 6 hours of ≥5, ≥10, and ≥15 letters comparing POS + LDP to POS alone, placebo + LDP, and placebo alone

Safety Endpoints

• Subjective ocular tolerability¹
• Conjunctival hyperemia¹
• Intraocular pressure (IOP)¹
• Biomicroscopy¹
• Ophthalmoscopy¹
• Systemic safety, as measured by HR and BP²
• Adverse events (AEs)¹ and serious adverse events (SAEs)²