Currently, miotics are taking center stage for treating presbyopia.
Reviewed by Kavitha Sivaraman, MD
Presbyopia correction has been garnering a great deal of attention. Kavitha Sivaraman, MD, Medical Director at the Cincinnati Eye Institute, Cincinnati, discussed the options that are available to patients and an exciting technology that is in the pipeline at the 2023 Women in Ophthalmology Summer Symposium, Marco Island, FL.
Currently, miotics are taking center stage for treating presbyopia. These include pilocarpine, aceclidine + brimonidine (Lenz Therapeutics) CSF-1 (Orasis Pharmaceuticals), and phentolamine + pilocarpine (Ocuphire Pharma) These drugs are in various investigatory stages of phase III clinical trials.
Miotic drugs work by producing a pinhole effect that increases the depth of focus and by contracting the ciliary muscle, which in turn increases accommodation. However, both actions are associated with side effects: the former with dim vision, nyctalopia, and restricted peripheral vision and the latter with headaches and peripheral retinal traction. Other complaints include conjunctival injection, ocular inflammation, and accommodative spasm, Sivaraman reported.
In 2021, VUITY (pilocarpine hydrochloride ophthalmic solution, 1.25% AbbVie) became the first miotic for presbyopia to receive FDA approval. The results of the GEMINI 1 and 2 trials showed that the incidence of headache at around 15% of participants. Other side effects were largely mild to moderate in severity.
A strategy that researchers are using to reduce side effects associated with use of miotics is to combine a miotic with another agent. On example is aceclidine plus tropicamide. Aceclidine is a muscarinic agonist that is less potent than pilocarpine, and tropicamide exerts a antimuscarinic effect that allows dilation without a significant impact on accommodation, she explained.
Another example is the combination of pilocarpinewith oxymetazoline, an alpha-adrenergic agonist that causes vasoconstriction and mydriasis. This product has the potential to reduce hyperemia, but also reduced the depth of focus because of the effect on the pupillary size, she commented.1
Another exciting approach to presbyopic correction is with lens softening agents, such as Novartis’ UNR844(lipoic acid choline ester 1.5%).
The theory behind this approach, Dr. Sivaraman explained, is that normal accommodation occurs due to central displacement of cytosol proteins in the crystalline lens fibers. Oxidative stress with aging results in formation of disulfide bonds between the lens proteins leading to impaired flow of cytosol, lens stiffening, and presbyopia.Lipoic acid, a prodrug that hydrolyzes disulfide bonds in its active form, can potentially lead to softening of the crystalline lens and improved elasticity.2
In their study, the investigators observed significant changes over an extended period (301 days) in the distance corrected near visual acuity compared with baseline compared with placebo.
Although initial phase 2 studies were promising, this particular compound failed to meet its primary endpoints in phase 2B clinical studies.
The take-home points were as follows: