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Vision changes that occur at middle age tend to be a major milestone for emmetropic patients. Unlike people who already wear glasses or contact lenses (and who can simply switch to progressives or multifocals as presbyopia begins), emmetropic presbyopes find themselves needing vision correction for the first time in their lives. Others may have once worn glasses and spent thousands of dollars on LASIK to get out of them, only to find themselves needing glasses again in middle age.

After age 40, emmetropes start to notice that they’re having trouble reading fine print. They hold things farther away to read them or increase the text size on electronic devices. Reading and other fine tasks can cause fatigue and eye strain. The mechanism of ciliary muscles acting on zonules to change the shape of the natural lens, with the help of the elastic spring forces of the Bruch’s membrane choroid complex (BMCC) seamlessly adjusting the dynamic range of focus (DRoF), no longer functions as it used to in a younger, more flexible system. There is currently no treatment to restore this mechanism.

Often, these patients are unhappy with this reality check of aging and do not want to wear reading glasses, which is why practitioners and industry are always looking for ways to help. The challenge is to develop therapies that correct presbyopia while maintaining the emmetrope’s clear distance vision.

Presbyopia Therapies Strike a Balance

Any treatment that changes the optics to improve near vision also has some effect on distance vision, so the challenge is to minimize degradation of the good distance vision enjoyed by emmetropes. The first and simplest solution — readers that patients put on and take off — are fine for some but not for all. The effort to give emmetropes the freedom they’re used to having has produced a range of different approaches:  

• Glasses and contact lenses — Reading glasses are the easiest and most economical solution for emmetropic presbyopia, but despite widespread availability of attractive frames, many emmetropes cannot stand them. The near power blurs distance vision, so patients need to put on readers for near tasks and remove them at other times. People tend to lose them, so it’s common to keep multiple pairs in the home, office and car (or around their neck). Emmetropic presbyopes can wear progressive eyeglasses with no power on top, allowing them to keep their glasses on for distance vision, but new eyeglass wearers may not want to wear glasses all the time.
  
  Contact lens options require a bigger tradeoff. There are two choices: monovision with a monofocal contact lens for near vision, leaving distance vision to the uncorrected eye (which is often not tolerated); or a multifocal contact lens, which compromises the quality of distance vision.
  

• Pupil-constricting eyedrops — The first presbyopia pharmaceutical therapy to rely on miosis reached the market a few years ago, offering patients the opportunity to improve near vision with an eyedrop. As a miotic agent causes pupil contraction, it creates a pinhole effect in which unfocused light is blocked and the remaining central light offers crisper near vision. The effect lasts for hours, but not all day.
  
  In addition to pilocarpine hydrochloride 1.25% (Vuity, AbbVie), we may soon see some alternatives on the market, including a pilocarpine 0.4% drop from Orasis,¹ an aceclidine drop from Lenz Therapeutics,² a phentolamine solution from Ocuphire³ and a carbachol/brimonidine combination from Visus Therapeutics.⁴
  
  Side effects of pilocarpine have included headaches as well as problems with night driving and other activities caused by dim vision.^5,6 When Vuity labeling was updated to reflect blurred vision from accommodative spasm; dim vision due to miosis; and risk of retinal detachment or retinal tears — especially in patients with a history of retinal pathology — an ASCRS consensus statement recommended evaluating patients for risk of retinal complications before prescribing Vuity.⁷ 
  

• Refractive surgery — Emmetropic presbyopes have a few surgical options. LASIK can be used with a classic monovision approach wherein the non-dominant eye is targeted to –1.50 D for near vision, but there is a corresponding sacrifice in distance vision for that eye, as well as anisometropia and decreased instereoacuity binocularly. A modified monovision approach with LASIK can be employed by manipulating spherical aberration with options such as Supracor (Bausch + Lomb), PresbyMax (Schwind) and Presbyond (Zeiss). Clear lens exchange (CLE) with a multifocal IOL or an extended depth of focus (EDOF) IOL can correct near vision, but patients sacrifice some of their distance sharpness because the optics of the eye are changed.
  
  
• Scleral therapy — Instead of changing the optics of presbyopia, an investigational laser therapeutic approach called laser scleral microporation (LSM) focuses on reducing the age-related stiffening of the sclera that prevents natural accommodative movement of the ciliary muscles, lens, choroid and other anatomy involved in the dynamic focusing function of the eye. Using an Er:YAG laser and scanner, the surgeon creates a matrix of micropores in the sclera and outside the visual axis in each of the four oblique quadrants. The laser treatment takes a total of about 5 minutes per eye.
  
  The 2-year pilot study for this procedure found that LSM caused no serious complications or pain.⁸ Since LSM does not touch the optics of the eye, patients’ distance vision, corneal topography and mean refractive spherical equivalent (MRSE) are not affected. All patients saw statistically significant changes in their dynamic range of focus (DROF); 73% expressed improved quality of life and satisfaction with near visual functions; and 97% experienced intermediate visual function (for activities of daily living, such as using the computer or mobile phone and reading) of 20/40 or better. Because LSM is a quick, painless procedure and ultra minimally invasive, it can be performed in the office. Future goals include studying the effects of progressive scleral aging, and efforts are underway to develop algorithms for customizing LSM effect and longevity as the eyes continue to age. The evolution of the technology has the potential to enable precision-medicine treatments throughout the lifecycle of the progressive age-related vision loss that is a hallmark of presbyopia.
  

Future Directions for Presbyopia

Given all the challenges of treating presbyopia while maintaining the emmetropic patient’s naturally clear distance vision, it’s understandable that many patients opt to tough it out with reading glasses. But there are many options in the pipeline to help patients facing this unwelcome part of aging, driving numerous predictions of market expansion for presbyopia care.^9,10 New pupil-constricting drop formulations could change how we use that modality. New multifocal contact lenses and IOLs continue to enter the market. Once LSM becomes an approved procedure, we could improve age-related effects on accommodative movement without touching the optics. Ultimately, we hope to find options to satisfy emmetropic presbyopes’ desire for both freedom and clear vision. 

REFERENCES

1. Orasis Announces Licensing Agreement with Optus Pharmaceuticals for Commercialization of Qlosi Eye Drops in Korea. Visionmonday.com. Published October 17, 2024. Accessed October 23, 2024. https://www.visionmonday.com/eyecare/article/orasis-announces-licensing-agreement-with-optus-pharmaceuticals-for-commercialization-of-qlosi-eye-drops-in-korea/

2. LENZ Therapeutics, Inc. LENZ Therapeutics Announces FDA Acceptance of New Drug Application for LNZ100 for the Treatment of Presbyopia. GlobeNewswire News Room. October 21, 2024. Accessed October 23, 2024. https://www.globenewswire.com/news-release/2024/10/21/2966144/0/en/LENZ-Therapeutics-Announces-FDA-Acceptance-of-New-Drug-Application-for-LNZ100-for-the-Treatment-of-Presbyopia.html

3. First subjects dosed in phase 3 trial of phentolamine ophthalmic solution for presbyopia. Healio.com. Published September 6, 2024. Accessed October 23, 2024. https://www.healio.com/news/ophthalmology/20240906/first-subjects-dosed-in-phase-3-trial-of-phentolamine-ophthalmic-solution-for-presbyopia

4. Hutton D. Visus Therapeutics presents topline clinical data from Phase 3 pivotal BRIO-I Trial of BRIMOCHOL PF for treatment of presbyopia. Ophthalmology Times. May 4, 2023. Accessed October 23, 2024. https://www.ophthalmologytimes.com/view/visus-therapeutics-presents-topline-clinical-data-from-phase-3-pivotal-brio-i-trial-of-brimochol-pf-for-treatment-of-presbyopia

5. Tucker T, Early J. Pilocarpine 1.25% Ophthalmic Solution (Vuity) for the Treatment of Presbyopia. American Family Physician. 2023;107(6):659-660. Accessed October 23, 2024. https://www.aafp.org/pubs/afp/issues/2023/0600/steps-pilocarpine-presbyopia.html

6. Waring GO 4th, Brujic M, McGee S, et al. Impact of presbyopia treatment pilocarpine hydrochloride 1.25% on night-driving performance. Clin Exp Optom. 2024;107(6):665-672.

7. ASCRS Consensus Statement on VUITY. Ascrs.org. 2024. Accessed October 23, 2024. https://ascrs.org/clinical-education/clinical-reports/2022-ascrs-consensus-statement-on-vuity

8. Ang RT. Two-year results of laser scleral microporation. Ophthalmology Times. 2023;48. Accessed October 23, 2024. https://www.ophthalmologytimes.com/view/two-year-results-of-laser-scleral-microporation

9. Presbyopia Market to Reach a CAGR of 3.29% during 2024-2034, Impelled by Ongoing Advancements in Intraocular Lens Implants. BioSpace. August 2024. Accessed October 23, 2024. https://www.biospace.com/presbyopia-market-to-reach-a-cagr-of-3-29-during-2024-2034-impelled-by-ongoing-advancements-in-intraocular-lens-implants

10. ABNewswire. Presbyopia Market on Track for Major Expansion by 2034, According to DelveInsight | Eyenovia, Orasis Pharma, O. openPR.com. October 16, 2024. Accessed October 23, 2024. https://www.openpr.com/news/3696593/presbyopia-market-on-track-for-major-expansion-by-2034

Robert Ang, MD is head of cornea and refractive surgery services at the Asian Eye Institute in Makati City, Philippines. He was fellowship trained in glaucoma, cornea and refractive surgery at the Massachusetts Eye and Ear Infirmary of Harvard Medical School. He discloses relationships with Ace Vision Group; Bausch and Lomb; BVI; Glaukos; Hoya; Johnson and Johnson; STAAR Surgical; and ViaLase.