Will a miotic agent or an agent that restores lens elasticity be more of an impactful pharmacologic therapy to treat presbyopia?
Click here to read the Cover Story to this Point/Counter.
Miotics are promising
One of these two pharmacologic approaches to the nonsurgical treatment of presbyopia includes PRX ophthalmic solution (Presbyopia Therapies). PRX eye drops are based on discoveries combining a proprietary vehicle with unique miotic combinations, without using pilocarpine. The drops are intended to induce strong miosis to create a significant pinhole effect with depth of field enhancement, without any associated accommodative distance blur.
In a recently completed randomized, double-masked, placebo-controlled phase 2b study, PRX achieved primary efficacy and safety endpoints for the treatment of presbyopia compared with placebo in patients ranging from age 48 to 64 years. At 30 minutes after instillation, 53% of study eyes gained at least three lines (P < .0001), and at 1 hour after instillation, 47% of study eyes gained at least three lines (P < .0001); 91.7% gained at least two lines of improvement in near vision (P < .0001). Approximately one-half of study eyes maintained a two-line or greater improvement up to 7 hours. Binocular near vision equaled or exceeded what was achieved monocularly with no significant loss of best corrected distance visual acuity. This unique drug was also well-tolerated with no serious adverse events.
With an estimated 1.8 billion people worldwide with presbyopia, including more than 110 million in the U.S. alone, and no FDA-approved pharmaceutical treatments available for presbyopia, the option of having an effective, safe, reversible, nonsurgical treatment for this condition would certainly meet an unmet need. With PRX in particular, this eye drop treatment would give patients the control of daily, convenient, bilateral use with a quick onset and temporary duration of effect in photopic and mesopic conditions. Miotic agents such as PRX could also serve a complementary role to currently available treatment modalities for presbyopia (for example, glasses, contact lenses, refractive procedures such as PRK/LASIK/SMILE, monofocal and presbyopia-correcting IOLs) to enhance either monovision or bilateral near vision. The potential therapeutic indications for a pinhole effect could be beneficial as well in patients with compromised vision quality due to corneal scars (ie, trauma or radial keratotomy) and decentered ablations. Finally, agents such as PRX could complement other investigational pharmacologic treatments for presbyopia with different mechanisms of action, such as EV06 (Novartis), which is designed to soften the natural lens. Given the recent clinical trial data of PRX, which demonstrated a statistically significant and clinically meaningful improvement in near visual function within 30 minutes, the future for miotic agents looks impactful, promising and bright.
Terry Kim, MD, is an OSN Cornea/External Disease Board Member. Disclosure: Kim reports he has a financial interest with Presbyopia Therapies.
Restoring lens elasticity
A pharmacologic agent that restores lens elasticity is of significant interest because presbyopia eventually affects everyone. The lens becomes rigid or stiff, loses elasticity, and can no longer flex or change shape, so we can no longer focus and see up close. Restoring elasticity, in particular, gets at the root of the problem. Miotics, on the other hand, work differently, by reducing the size of the pupil.
If we could restore that elasticity — halt the progression of the condition — we would be able to keep the eye youthful and could affect virtually everyone.
An agent that can potentially restore lens elasticity may work in a way to also prevent cross-linking from occurring. We talk about cross-linking in other eye diseases, specifically in regard to conditions in the cornea, but when you think about the lens also having its own natural cross-linking, which causes stiffening of the lens, it is interesting to think about a drug that prevents this cross-linking effect that could restore or preserve the elasticity of the lens.
Kathryn M. Hatch, MD, is an OSN Technology Board Member. Disclosure: Hatch report no relevant financial disclosures.
The holy grail of refractive surgery
Finding an effective treatment for presbyopia is the holy grail of refractive surgery, especially with an aging population. Most patients would prefer a noninvasive, reversible, low-risk treatment, and topical drops such as miotics are possible candidates for this. We know from cataract and refractive lensectomies (RLE) that the crystalline lens gets stiffer with age. There are some potential treatments to reverse the stiffening of the lens, but until those are available, we can view miotics as buying time for those wanting to delay the effects of presbyopia.
The question posed is if miotics will be “more” impactful, but to what? Currently we have no approved pharmacologic treatments for presbyopia. Bifocal contacts, multifocal/progressive lenses in glasses and monovision contacts are all widely used treatments for presbyopia. However, LASIK patients and those with other corneal refractive surgeries want to maintain the glasses/contact lens-free visual improvement they have achieved and typically are often bothered by presbyopia. RLE also offers a great alternative for those who want to treat presbyopia with or without concurrent refractive error. However, patients best appreciate RLE when the presbyopia is advanced, not in the early stages. Topical miotic drops may be a nice initial step to treat and delay the effects of presbyopia until the presbyopia is advanced and patients reach the point that RLE with either extended depth of focus or standard multifocal lenses is better appreciated.
Of course, a treatment that restores lens elasticity without causing lens opacities or optical disturbances would be the ideal treatment and not involve potential changes to the pupil. The question with that type of treatment will be, what about the increasing volume of the crystalline lens that continues throughout life? How will that affect vision and accommodation even if the lens retains elasticity?
Francis W. Price Jr., MD, is an OSN Cornea/External Disease Board Member. Disclosure: Price reports he is a consultant for Alcon and Allergan and is currently conducting a presbyopia study with Allergan.