Presbyopia – A Review of Current Treatment Options and Emerging Therapies

Figures & data

Table 1 Current Surgical Options for Presbyopia

Site	Surgical Options
Cornea^Citation65,Citation108^–^Citation110	Monovision (LASIK)
	Presbyopic LASIK* (multifocal laser ablation)
	Photorefractive keratectomy (PRK)
	Intracor Femtosecond Laser (LASIK)
	KAMRA^TM Corneal Inlay
	Conductive keratoplasty
Lens: refractive lens exchange^Citation26,Citation111	Monovision (monofocal IOL)
	Multifocal IOL
	Accommodative IOL
	Light adjustable lens
Sclera*^Citation75	VisAbility Micro-Insert scleral implant (Refocus Group, Dallas, TX, USA)
	Scleral laser anterior ciliary excision (LaserACE, Ace Vision Group, Newark, CA, USA)
	Scleral laser micro-excision

Note: *Not FDA-approved

Abbreviations: IOL, intraocular lens; LASIK, laser-assisted in situ keratomileusis.

Table 2 Topical Pharmacological Options Currently Under Investigation, Defined as Those Working via Pupil Modulation or Aiming to Restore Accommodation

Compound Name and Formulation	Mechanism of Action	Clinical Development Status	Key Findings	Manufacturer/ClinicalTrials.gov
Pupil modulation
Carbachol/brimonidine	Miotic	Phase 2	Statistically significant improvement in NVA over placebo; effect was maintained over 3 months (N=48)	Therapeutics press release 2020^Citation91 Abdelkader 2015^Citation90 Visus
FOV Tears (pilocarpine/phenylephrine/polyethyleneglycol/nepafenac/pheniramine/naphazoline)	Miotic	Phase 1; currently available in Columbia, with Phase 2 studies ongoing	Pupil size initially decreased and NVA improved up to 5 h (N=14)	Renna et al, 2016^Citation89
AGN-190584 ophthalmic solution (pilocarpine)	Miotic	Phase 3 complete FDA registration	A statistically significant greater proportion of participants treated with AGN-190584 gained 3 lines or more in mesopic, high contrast, binocular DCNVA (N=327)	Allergan press release 2020^Citation92 NCT03857542^Citation93
AGN-199201 ophthalmic solution (pilocarpine/oxymetazoline)	Miotic	Phase 2	Up to 70% of patients had at least a 2-line improvement in uncorrected NVA (N=151)	NCT02780115^Citation94
PRX ophthalmic solution (aceclidine/tropicamide)	Miotic	Phase 2b	Primary endpoint vs placebo was met; duration of effect was approximately 7 hrs	Presbyopia Therapies press release 2018^Citation95
Nyxol (phentolamine ophthalmic solution)/pilocarpine	Miotic	Phase 2	Primary endpoint is percentage of subjects with ≥ 15 letters of improvement in photopic binocular DCNVA	Ocuphire^Citation96 NCT04675151^Citation97
CSF-1	Miotic	Phase 2b complete	Statistically significant improvement in DCNVA of a 3-line or greater gain.	Orasis Pharmaceuticals press release^Citation98 NCT03885011^Citation99
VISION-1 (pilocarpine)	Miotic	Phase 3	Primary outcome is the proportion of subjects gaining ≥ 15 letters in mesopic, high contrast, binocular distance corrected near visual acuity (DCNVA) [Time Frame: 120 minutes post-dosing]	Eyenovia^Citation100 NCT04657172^Citation101
Treatments for the underlying cause of presbyopia
UNR844	Lipoic acid choline ester	Phase 1/2	Bilateral DCNVA improved, with 53.1% UNR844 vs 21.7% placebo subjects gaining ≥10 letters. Improvements in DCNVA were sustained at 5 and 7 months after UNR844 dosing ceased.	Novartis NCT02516306^Citation106
UNR844	Lipoic acid choline ester	Phase 2a	Bilateral DCNVA improved, with a four-letter median difference between UNR844 vs placebo groups (p = 0.0924), and no meaningful differences in side effects	Novartis NCT03809611^Citation105,Citation112

Notes: ≥, greater than or equal to; (DC)NVA, (distance-corrected) near vision acuity; N, study population sample size; P, statistically significance; vs, versus. This table only includes products for which clinical data is available.

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