No more reading glasses: daily eyedrops for presbyopia

Authors

Dr. Nawaaz Nathoo (biography and disclosures) and Sorayya Seddigh (biography and disclosures)

Disclosures: Therapeutic recommendations have not received regulatory approval, they are “off-label” use of medication in Canada. Mitigating potential bias: Recommendations are consistent with published guidelines approved by the US Food and Drug Administration (FDA) and with current practice patterns.

What frequently asked questions/gaps I have noticed

Presbyopia is a condition that affects all people, often becoming noticeable in the 40s. With age the crystalline lens hardens and begins to lose its elasticity, making the process of accommodation initially difficult and eventually impossible, creating challenges with focusing on near objects such as computer screens, reading material, etc.¹

Although it is not currently possible to stop or reverse this natural aging process, the refractive errors caused by presbyopia can be corrected with glasses, contact lenses, or surgery. However, a growing body of literature has increasingly turned to pharmacologic interventions to reduce the dependence on these refractive aids.² Recently, pilocarpine 1.25% eyedrops were approved by the US Food and Drug Administration (FDA) as a new therapy for presbyopia.³ The introduction of eyedrops represents a new horizon in presbyopia treatment, ushering in a new era of medical management options for patients.

Data that answers these questions/gaps

Over the last decade, numerous pharmacologic agents have been developed to improve the vision of patients with presbyopia. These drugs either induce miosis to create a pinhole effect; enhance depth of field; or attempt to restore the flexibility of the crystalline lens.⁴ The main active ingredient of the former category includes parasympathomimetic drops such as pilocarpine, carbachol, and physostigmine, sometimes in varying combinations with other drugs added in (e.g., NSAIDs, alpha-2 adrenergic agonists); these drugs are currently at various stages of development along the research pipeline.^4,5

In December 2021, pilocarpine hydrochloride 1.25% eyedrops (brand name Vuity) became the first drug approved by the FDA for the medical management of presbyopia.³ Pilocarpine is a miotic agent that uses the eyes’ natural ability to constrict the pupil via parasympathetic innervation. It has been shown to improve near-intermediate vision without impacting distance vision. Phase 3 trials (GEMINI1 and GEMINI2) showed that among adults aged 40–55 with presbyopia (n=750), daily eyedrops resulted in subjects gaining 3+ lines in low-light, high-contrast, binocular distance-corrected near visual acuity (DCNVA) on day 30.⁶ The most common adverse events (>5%) were mild headaches and eye redness. While other studies have reported rare occurrences of retinal detachment and ocular inflammation (<1%), none were documented in these clinical trials.⁷ Still, caution should be taken with patients who have a history of iritis or risk factors for retinal detachment (e.g., past history, family history, high myopia, etc.). Similarly, studies of pilocarpine hydrochloride 0.4% demonstrated promising results in the Phase 3 NEAR-1 and NEAR-2 clinical trials and is on the verge of commercialization in the US, while others like BRIMOCHOL (carbachol and brimonidine tartrate) are currently undergoing Phase 3 trials.^8,9

There are currently no eye drops for presbyopia treatment that have been approved for use in Canada.

What I recommend (practice tips)

Following diagnosis, it is important to establish a common understanding with your patients that presbyopia is a chronic progressive disease. While therapies improve visual acuity, they are not curative. Here is a simple approach to discussing treatment options with patients, from least to most invasive:¹⁰

1. Corrective glasses are the most common management strategy for presbyopia. Options include reading glasses, bifocals/trifocals, and progressive lenses. Some are available over-the-counter, but custom-made glasses are also an option for those with specific needs (e.g., astigmatism, anisometropia). Although glasses are the safest, most accessible, and least invasive method of treatment, many patients prefer to avoid glasses due to inconvenience and negative physical and psychosocial impact associated with using them.
2. Contact lenses (CL) are another form of management for presbyopia. Monovision CL correct the dominant eye for distance vision and the non-dominant eye for near vision; although this improves the range of vision (allowing for both distance and some near vision), depth perception and binocular vision will be impaired. In contrast, multifocal CL provide various approaches to providing multiple focal distances of clear vision, allowing the patient to focus on objects at various distances. Although CL’s avoid the negative psychosocial impact that glasses bring, CL tend to be more costly, require daily care, and increase risk of dry eyes and adverse events such as corneal infections.
3. Eye drops are a practical, non-invasive option for patients who wish to remain free of glasses and CL. Pilocarpine 1.25% is currently the only eyedrop that is approved by the FDA for presbyopia (one drop to each eye once/day). In Canada, pilocarpine would be an off-label use; commercially, a 2% formulation is the most readily available (although other concentrations can often be compounded on request). Long-term side effects of these drugs are under investigation for this indication, although pilocarpine drops have been used for decades in the treatment of glaucoma.¹¹ As discussed above, patients with iritis and risk of retinal detachment should use caution, and given that miosis can worsen vision in dim lighting, patients are advised to take caution when night driving. Given the preliminary nature of the current data and the lack of approval in Canada, it is recommended that ophthalmologists take the lead in prescribing and managing this off-label treatment option.
4. Refractive surgery offers a more permanent alternative, whereby patients undergo corneal or lens-based surgery. Corneal laser surgeries (e.g., LASIK, PRK) offer presbyopia correction through monovision, which has similar shortcomings as monovision CL. Lens-based surgeries include refractive lens exchange (RLE) and cataract surgery. These options tend to be more invasive and costly. Lens-based surgery can achieve either monovision (with many of the same benefits and limitations of CL-monovision discussed above) or multifocal intra-ocular lenses; these multifocal lenses allow multiple zones of focused vision but may lead to other difficulties with vision such as seeing halos/glare and imperfect quality of vision. Surgical techniques target presbyopia symptoms rather than restoring accommodative ability and are irreversible as the natural lens that is removed from the eye can never be replaced.

In summary, the FDA approval of pilocarpine eyedrops not only augments the physician’s toolkit, but also paves the way for new innovative methods of presbyopia management; numerous new pharmaceutical eyedrops are underway. These advancements suggest a bright future for adaptive and personalized vision correction solutions for patients with presbyopia.

References

1. Boyd K. What is presbyopia? American Academy of Ophthalmology. November 22, 2022. Accessed Aug 15, 2023. (View)
2. Renna A, Alió JL, Vejarano LF. Pharmacological treatments of presbyopia: a review of modern perspectives. Eye Vis. 2017;4(1):3. doi:10.1186/s40662-017-0068-8 (View)
3. Meghpara BB, Lee JK, Rapuano CJ, Mian SI, Ho AC. Pilocarpine 1.25% and the changing landscape of presbyopia treatment. Curr Opin Ophthalmol. 2022;33(4):269-274. doi:10.1097/ICU.0000000000000864 (View with CSPBC or UBC)
4. Grzybowski A, Markeviciute A, Zemaitiene R. A review of pharmacological presbyopia treatment. Asia Pac J Ophthalmol. 2020;9(3):226-233. doi:10.1097/APO.0000000000000297 (View)
5. Benozzi J, Benozzi G, Orman B. Presbyopia: a new potential pharmacological treatment. Med Hypothesis Discov Innov Ophthalmol. 2012;1(1):3-5. (View)
6. Waring GO, McCabe C, Wirta D. GEMINI 1 & 2 pooled phase 3 safety and efficacy: AGN-190584 primary and key secondary endpoints. Cataract Surgery “Telling It Like It Is” Meeting, Orlando, FL, USA. 2021.
7. Al-Khersan H, Flynn HW Jr, Townsend JH. Retinal detachments associated with topical pilocarpine use for presbyopia. Am J Ophthalmol. 2022;242:52-55. doi:10.1016/j.ajo.2022.05.011 (View with CPSBC or UBC)
8. Hutton D. FDA accepts Orasis Pharmaceuticals’ NDA for CSF-1 for treatment of presbyopia. Ophthalmology Times. February 21, 2023. Accessed Aug 15, 2023. (View)
9. Visus T. Safety and efficacy study of BRIMOCHOLTM in subjects with emmetropic phakic and pseudophakic presbyopia. October 3, 2022. Accessed Aug 15, 2023. (View)
10. Chuck RS, Jacobs DS, Lee JK, et al. Refractive errors & refractive surgery preferred practice pattern®. Ophthalmology. 2018;125(1):1-104. doi:10.1016/j.ophtha.2017.10.003 (Request with CPSBC or view with UBC)
11. Boger WP 3rd, Steinert RF, Puliafito CA, Pavan-Langston D. Clinical trial comparing timolol ophthalmic solution to pilocarpine in open-angle glaucoma. Am J Ophthalmol. 1978;86(1):8-18. doi:10.1016/0002-9394(78)90006-5 (Request with CSPBC or view on UBC)

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