International success with the Kamra inlay (AcuFocus) has demonstrated the clinical efficacy of a small aperture in expanding depth of focus to provide good near vision. While the Kamra is not yet available in the United Sates, results of the FDA clinical trial demonstrated good efficacy. Some US physicians have even had the device implanted in their own eyes. With its small aperture creating the optical effect at the corneal plane, a pinhole corneal inlay inevitably causes some degree of loss of contrast sensitivity. As a result, the Kamra inlay is recommended for unilateral implantation. But what if we could pharmacologically induce miosis of the pupil to achieve a similar effect at the natural optical stop of the eye? Clearly, we have had the ability to create small pupils for years with a variety of glaucoma medications. So, why hasn’t the use of miotics taken off as an off-label treatment for presbyopia?
The answer is that all previously available miotics suffer from an unacceptable constellation of side effects. Older ophthalmologists will recall the days of widespread miotic usage. Certainly these patients had good uncorrected near acuity, but their pupils were often smaller than the optimal 1.6-mm central aperture of a Kamra inlay. These patients also suffered from accommodative spasm, brow ache, myopic shifts, anterior segment inflammation, synechiae, pigment dispersion, and a number of other side effects owing to chronic muscarinic stimulation of the ciliary muscle and pupillary sphincter.1 Topical combinations of pilocarpine or carbachol along with an NSAID have been tried as a presbyopia treatment. The NSAID is intended to help prevent the inflammatory effects of the miotic. Unfortunately, this has no effect on accommodative spasm or the undesirable effects of chronic ciliary muscle stimulation.2 Agents such as pilocarpine and carbachol also tend to produce a pupil that varies somewhat in diameter throughout the dose-response curve. Over a period of several hours, the pupil may transition through a variety of diameters, either larger or smaller than the optimal size range for near and distance vision. The perfect topical agent for presbyopia would create a stable pupil of about 1.6 mm for several hours with no side effects.
While no medication is perfect, a potentially suitable candidate for treating presbyopia has been identified by a small company called Presbyopia Therapies, based in San Diego. The drop, known as PRX-100, quite simply creates miosis without accommodation. I am not yet at liberty to disclose the constituents of the drop; however, I can attest firsthand to the fact that it creates very functional near vision in presbyopes for about 8 hours. The drop is intended for bilateral use because it allows for very high-quality distance acuity. The effect occurs after approximately 15 minutes after instillation. Importantly, the pupil remains stable at approximately 1.6 to 1.9 mm throughout the duration of action.
STUDY RESULTS
A pilot study of PRX-100 in patients with a mean age of 51.3 years was performed by David Castillejos, MD, in Tijuana, Mexico. Nine individuals were treated bilaterally with the drop and achieved binocular mean distance-corrected near visual acuity at 14 inches of 20/22.7, equivalent to J1 to J1+. The interesting thing to me was that these patients did not report nighttime glare or halos, and, in fact, some reported that their uncorrected night vision was improved. Perhaps at the pupil size achieved, the light loss was trumped by the improved contrast sensitivity often seen with miosis. A US phase 2 trial is planned for 2015.
POTENTIAL LIMITATIONS
There are several possible limitations to the use of this drug. Patients have reported redness and stinging upon instillation. Patients may also notice some indoor dimming during the first few days of use, although this seems to go away with continued use. The effect is only temporary and, in most patients, only lasts about 8 hours. Finally, it remains to be seen if differing effects will be seen in patients with different degrees of iris pigmentation.
CONCLUSION
Our patients have made it very clear to us that they will resort to almost anything to rid themselves of presbyopia. Other than spectacles and contacts, all of our treatment options are currently surgical in nature. If successful, a pharmacologic approach to presbyopia would be a welcome addition.
1. Zimmerman TJ, Wheeler TM. Miotics: side effects and ways to avoid them. Ophthalmology. 1982;89(1):76-80.
2. Benozzi J, Benozzi G, Orman B. Presbyopia: a new potential pharmacological treatment. Med Hypothesis Discov Innov Ophthalmol. 2012;1(1):3-5.
