Article

So Many Options Coming! What Differences Do We See So Far?

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THE PRESBYOPIA DROP FLOODGATES are opening over the next few years. With so many options in the pipeline and awaiting FDA approval, the decision of which drop for whom will soon be better understood. Since many of the presbyopia drops are very similar, we wanted to focus on their differences and unique proprietary vehicle formulations, which may give us perspective on the patients for whom these products will work well.

Many of the drop formulations, including Vuity (1.25%, Allergan/AbbVie), which is currently the only presbyopia drop that is FDA approved, utilize the drug pilocarpine. Pilocarpine is a cholinergic muscarinic receptor agonist that activates muscarinic receptors located on smooth muscles of the iris sphincter and ciliary muscle. This causes activation of the iris sphincter and decrease of the pupil size, resulting in an increase in depth of focus, known as the “pinhole effect.”

Of drops in this category, utilizing varying percentages of pilocarpine, we find the following as points of interest and differentiation between them:

  • Vuity (Allergan/AbbVie): The pHast technology allows the pilocarpine HCL to rapidly adjust to the pH of the tear film, resulting in increased corneal penetration.1
  • CSF-1 (Orasis): This is a preservative-free formulation with proprietary vehicle to allow for an optimal balance among efficacy, safety, and comfort.2
  • MicroLine (Eyenovia): The Optejet, with MAP technology, uniquely administers the medication as a spray into the eye vs a drop.3
  • GLK-302 (Glaukos): This compound utilizes iLution, a cream-based delivery of pilocarpine applied to the outer surface of the eyelid. It allows for transdermal delivery applied topically to the skin.4
Another molecule utilizes a novel mechanism of action alone and in combination with pilocarpine:
  • Nyxol or Nyxol + low-dose pilocarpine (Ocuphire): Nyxol is preservative-free and utilizes 0.75% phentolamine, an alpha 1 adrenergic antagonist that inhibits contraction of the iris dilator muscle with a long-lasting durability. A second product adds 0.4% pilocarpine, which activates the iris sphincter muscle.5
Others are utilizing brimonidine tartrate, which is a sympatholytic alpha-2 agonist. It inhibits iris dilator muscle contraction and may also inhibit contraction of the ciliary muscle by activating alpha-2 receptors. Brimonidine also helps with increasing bioavailability and duration of action of other ingredients by altering aqueous dynamics. These include:
  • LNZ100/LNZ101 (Lenz Therapeutics): LNZ100 utilizes aceclidine only, which has been shown to target the iris sphincter only and avoid ciliary muscle activation.6 LNZ101 is a mix of aceclidine and brimonidine for a combined effect.6
  • Brimochol (Visus): Brimochol is combination of carbachol and brimonidine tartrate. Carbachol is a parasympathomimetic that mimics the effect of acetylcholine on both muscarinic and nicotinic receptors in the iris sphincter muscle, activating it to decrease the pupil size for the “pinhole effect.”7
Last but not least, there is a whole other ballgame:
  • Dioptin (Novartis): This lipoic acid-based drop is metabolized by the crystalline lens to help reduce the disulfide bonds between proteins that develop with age and restore elasticity and accommodative ability.8

When we look at these differences we can begin to see how each may have different applications for patients, for instance, avoiding preservatives in patients with ocular surface disease or providing a spray for patients who have dexterity issues. As more data are released and FDA approval is gained by each, we will be able to have a different conversation regarding efficacy in patient types. Until then, keep sitting on the edge of your seats. We will be back to deliver that discussion sooner than you think. ■

References

  1. Vuity product information. Vuity website. Accessed April 20, 2022. https://www.vuitypro.com/innovation .
  2. CSF-1 overview. Orasis Pharmaceuticals website. Accessed April 20, 2022. https://www.orasis-pharma.com/our-solution/csf-1-overview/ .
  3. Eyenovia pipeline: MicroLine (presbyopia). Eyenovia website. Accessed April 21, 2022. https://eyenovia.com/pipeline/presbyopia/ .
  4. Ophthalmic innovation. Glaukos website. Accessed April 21, 2022. https://www.glaukos.com/about-us/innovation/ .
  5. Nyxol. Ocuphire website. Accessed April 21, 2022. https://www.ocuphire.com/product-pipeline/nyxol .
  6. Pipeline. Lenz Therapeutics website. Accessed April 21, 2022. https://lenz-tx.com/pipeline/aceclidine/ .
  7. A novel, combination eye drop. Visus Therapeutics website. Accessed April 21, 2022. https://www.visustx.com/brimochol .
  8. Richdale K, Wirta D, Venkataraman S, Zhu A, Shettle L. UNR844 ophthalmic solution for the topical treatment of presbyopia: results of a phase ii randomized controlled trial. Paper presented: Annual meeting of the American Academy of Optometry; October 7, 2020; Virtual.