Disclosures: Donnenfeld reports he is a consultant for Allergan, Alcon, Novartis and Visus and has financial interest in Orasis and Visus. Trattler reports he is a consultant for Allergan, Alcon and Visus and has financial interest in Orasis and Visus.
October 20, 2020
3 min read

Combination drop among topical presbyopia treatments in development

Pipeline holds promise for expanding treatment options.

Disclosures: Donnenfeld reports he is a consultant for Allergan, Alcon, Novartis and Visus and has financial interest in Orasis and Visus. Trattler reports he is a consultant for Allergan, Alcon and Visus and has financial interest in Orasis and Visus.
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An estimated 128.5 million people are expected to be presbyopic in the United States by 2023.

Both established industry players and clinical-stage companies are increasingly focused on expanding presbyopia treatment options, with the hope of improving patient satisfaction in this important demographic group.

Eric D. Donnenfeld
Eric D. Donnenfeld
William B. Trattler
William B. Trattler

The COVID-19 pandemic has made wearing reading glasses even more problematic due to fogging of glasses while wearing masks, further highlighting for patients the value of a pharmacologic treatment for presbyopia that could reduce their dependence on glasses.

We all have many patients with loss of accommodation who do not like wearing reading glasses, but they may not be quite ready for invasive lenticular surgery. A new category of presbyopia-correcting topical drops currently in development has great potential for this group of patients.

Among the topical therapies being investigated is a unique combination from Visus Therapeutics, which recently acquired the patents and is leading late-stage clinical development for a combination miotic/alpha-2 agonist drop discovered by renowned ophthalmologist and innovator Herb Kaufman, MD. Visus joins Allergan, Orasis Pharmaceuticals and Presbyopia Therapies in the quest to bring a pupillary miotic to market, while Novartis and ViewPoint Therapeutics are undertaking development of topical therapies that aim to correct near visual acuity by restoring accommodation to the crystalline lens.

These treatments could exponentially expand our toolbox for assisting patients in maintaining functional vision as they age, and we predict many of them could be used either in succession over time or interchangeably, based on a patient’s lifestyle.

An interesting combination

Visus Therapeutics’ entrant to the space is a combination of carbachol, a long-acting miotic that creates a pinhole effect with the goal of increasing depth of field, and brimonidine tartrate, a sympatholytic alpha-2 agonist that has been previously shown to prevent iris dilation and inhibit ciliary body contraction. Three published studies collectively demonstrate the potential of this combination drop and have informed the pivotal trial plan, slated to commence in 2021.

Because carbachol is known to be the most potent and sustained-action cholinergic for pupil constriction, it is not surprising that early studies of the carbachol/brimonidine combination have demonstrated duration of 8 to 12 hours and near visual acuity improvement of more than 5 Jaeger lines. In developing this combination, Kaufman intended for the two components to have complementary actions. The addition of brimonidine may be able to mitigate some of the side effects typically associated with cholinergic agents on the ciliary body, such as headache, browache and myopic shift. Additionally, it is also hoped that brimonidine may potentiate and prolong the pinhole effect of carbachol on the iris sphincter muscle by altering aqueous dynamics.

Thus far, clinical data on all these topical approaches are limited, as there are no phase 3 study results available yet.

Patient considerations

When we think about patients who are most bothered by their degradation in near vision, many of them are working professionals, so their No. 1 priority in a topical presbyopia drop will likely be duration of effect. It will be ideal for a drop to last throughout a full workday. In addition, most patients, when given the choice, tend to avoid eye drops that need to be taken multiple times per day.

Tolerability will also certainly come into play, given what we know about the side effects of these medications from their historical usage as glaucoma treatments. Approaches that mitigate miotic-induced side effects such as hyperemia and headache will likely prove beneficial for patient acceptance.

We also do not yet know how any of these formulations will be preserved. There is significant overlap between presbyopes and those with ocular surface disease. If presbyopia-correcting drops end up containing benzalkonium chloride (BAK), we would lean toward recommending a longer-lasting drop, especially for patients who have ocular surface disease or are already on other preserved topical medications, to reduce their BAK exposure.

Finally, of course, the degree of near visual acuity improvement — especially in comparison to more traditional options — will be important to patients, as well.

Evaluating which drop option, if any, is a fit for a given patient will depend on all of these factors, as well as any contraindications. As with other refractive options we present to patients, presbyopia-correcting drops will need to be incorporated on an individual basis, based on discussions about patients’ lifestyle, vision demands and expectations. We can all agree, however, that this is an exciting developing treatment category, with the potential to offer our patients noninvasive correction of presbyopia and increased spectacle independence.