I REMEMBER YEARS AGO FIRST hearing about presbyopia drops. I was very impressed with the mechanism of action and early proof of concept studies. Shortly after, I was invited to be part of the clinical studies. Then, I read the inclusion and exclusion criteria. In retrospect, they were among the narrowest criteria I have ever seen. I was thinking, “How in the world am I going to find patients that fit the criteria?”
Well, somehow we did meet full enrollment for this and subsequent studies. Why do I bring this up? First, the earlier studies were designed to take advantage of the best aspects of the drops. This means choosing the patients whom they feel will experience the greatest success—or in other words, patient selection. I think more than anything else, patient selection is extremely important with presbyopia drops.
Let’s start off with the slam dunk patients—the patients who were in the early clinical studies. They were emmetropes with a low to moderate add. Zero refractive error at distance works the best with a miotic drop. I remember a conversation years ago with the presbyopia contact lens guru Dr. Pete Kollbaum from Indiana University. He helped design presbyopia contact lenses for a major manufacturer. I asked him why the lens system that he designed only had about +1.50D difference between the eyes (one distance biased, the other near bias). Essentially, there was a total of +1.50D add power in his system. What about the +2.50D add presbyope? Pete went on to explain that the pupil size gets smaller and makes up the difference. In other words, for a +2.50D add, the contact lens picks up +1.00D to +1.50D, and miosis picks up another +1.00D to +1.50D. There is variability in the contact lens add because the lens is aspheric. That was my introduction to how a small pupil can be used to optimize a presbyopic treatment—because smart Pete said so.
So what was the lesson I learned? Miosis is worth about +1.50D add. Therefore, going back to patient selection, I use the +1.50D add as a rule of thumb. This drop will give the right patient about a +1.50D add. This translated into the original narrow inclusion/exclusion criteria I talked about earlier. The early clinical studies had an age requirement, something like 40-50 years old. Why? Because you don’t want a +2.50D add patient.
As noted, emmetropes are at the top of the list for these drops. Other refractive errors would work too, but keep in mind that the patient must be distance corrected. Would I put a -2.00D in the drop? No way: the quality of near vision with the drop usually will not be as good as no correction at all for these types of patients. How about a -9.00D? Not a chance: unless the patient wants to wear his or her distance lenses or contacts, the drop is not going to work. Of course, there will always be exceptions.
Now, I have found, outside of the clinical studies, that I can place patients beyond 50 years old successfully in the drops. It really depends on visual demand or, in clinical parlance, working distance. Therefore, if the “older” presbyopic patient looks at an 18- to 20-inch distance from the screen, simple math says all you need is about a +1.50D add. Or how many times have you seen patients hold their phone at about 20 inches anyway? It’s something to consider.
One aspect of the early clinical studies was establishing how long the drop lasts. In those early studies, we had to keep the patients in our office for 10-12 hours, and they were not supposed to leave. My study staff referred to it as patient imprisonment. We had to test the patient minutes after instillation of the drops and at hourly intervals for 10 visits. One of the investigators at another site told me that they brought in Barcalounger chairs for the patients. I wasn’t smart enough to think of that. Luckily, the later studies did not require that much contact time. The current rule of thumb is about 4 hours of efficacy. The newer drops might establish longer times or go to twice-a-day dosing.
Then, the studies had a pupil size guardrail. Large pupils were not allowed in the studies. The studies showed high success rates with the drops. I really think that pupil size makes a huge difference between success and failure in the real world. I heard somewhere that the optimum pupil size was 2-3mm for near vision. Here is where the guardrail worked in the clinical trials. If the patient had a large, say 9mm, pupil, the drops would probably not be able to bring the size into the optimal range. The patient would probably be left with a pupil that was too large, and you wouldn’t get much, if any, near effect. I heard stories about the drops not working very well. I really don’t think people look at the pupil size prior to using the drops. Now, don’t get me wrong—there are other reasons for failure (like I covered before). But I think pupil size needs to be considered when selecting patients. Conversely, how about a small pupil to begin with? Well, it could be another factor for “failure.” Getting the pupil to less than 2mm in size can take away near and also distance efficacy.
Regarding pupil size, I was really concerned about the effect on night distance vision. With smaller pupils and lower light levels, it sounded like a recipe for disaster. I was absolutely shocked to see that some of the patients’ night vision improved over their normal vision. Some were clocking down to 20/10 vision. Go figure.
Then there is the elephant in the room—vitreoretinal problems. Avoiding many potential retinal problems just takes common sense—things we learned back in school, such as high myopia, a history of retinal conditions, etc. I hear some of my colleagues not only require a retinal exam but also optical coherence tomography. They want to see if there are any pre-existing vitreous conditions prior to prescribing the drops.
Back to patient selection: as I said before, for myself, the most highly successful patient is the low to moderate emmetrope. The inventors of the drops knew this and designed the earlier studies to reflect it. Now, I could go outside of the perfect patient, but in doing so, the rate of success decreases. Nonetheless, one could still have a successful patient. Greater refractive errors, larger or smaller pupils, the working distance of the patient, how many hours the patient needs near vision, etc., are all factors that influence the success rate.
Now, you may have patients that have all of these factors going against them, they are well outside the profile of the perfect patent, but yet they succeed. Taking a cue from contact lenses, patient motivation is the X factor. High motivation can push everything into the success category. An example is a patient not wanting to wear reading glasses on a date. I have had patients, despite all the factors stated before going against them, succeed because they were extremely motivated. The X factor was at work. ■