August 2016




Pharmaceutical focus

Close-up on presbyopia study

by Maxine Lipner EyeWorld Senior Contributing Writer


Reviewing miotic approach to presbyopia

New technology may not be the only way to compensate for the woes of presbyopia. Innovative miotics may provide a pharmacologic option for those who prefer to avoid surgical intervention. In a recent study published in Eye & Contact Lens,1 investigators considered whether use of the alpha agonist brimonidine together with the parasympathomimetic drug carbachol might result in miosis, which could help lessen the effects of presbyopia. EyeWorld asked 2 leading practitioners to consider the study and share their impressions here. The aim of the prospective, randomized placebo-controlled clinical trial was to determine whether presbyopia could be alleviated with the aid of miosis created by using carbachol in conjunction with brimonidine. Included in the study were 48 subjects between the ages of 43 and 56 who were both emmetropic and presbyopic. Investigators divided subjects into 2 groups. The 30 eyes in the “treatment group” received 0.2% brimonidine eye drops in conjunction with a dose of 2.25% carbachol. Meanwhile, the 18 eyes in the control group received placebo drops. All drops were placed in the non-dominant eye in a masked fashion. Investigators found a statistically significant improvement in near acuity for all who had received the brimonidine in conjunction with the carbachol. This was not true for any who were given the placebo. Investigators saw nothing to indicate that tolerance toward the drops was developing during the study period.

After each group was subdivided into those age 50 and older and those under 50, investigators found that the older group’s mean near acuity improved from J7 before instillation of the drops to J3 at 1 hour after usage and remained there at the 2-hour mark. At 4 hours this dropped to J4, and at 10 hours was at J5. The mean pupil size decreased significantly from a mean of 4.77 mm before treatment to 2.5 mm at 1 hour. At the 10-hour mark, this was at 3.81 mm. Meanwhile, for those in the younger group, visual acuity likewise significantly improved from a mean of J6 before treatment to J2 at the 1-hour mark. By 10 hours after treatment, this had fallen to J5. Before treatment the mean pupil size was at 4.72 mm and 1 hour after was at 2.71 mm. By 10 hours the mean was 3.85 mm. The masked placebo group saw no significant difference in mean pupil size or near visual acuity. Distance acuity for all patients was at 20/20 prior to and throughout treatment.

Investigators concluded that making the pupil smaller improves depth of focus, which in emmetropic presbyopic patients significantly improves near visual acuity. They view the combination of brimonidine and carbachol as a safe and acceptable alternative to surgical presbyopia correction or traditional lenses. Daniel Chang, MD, Bakersfield, California, said using drops to alleviate presbyopia is an exciting approach and might provide an alternative for some. “I think there is amazing presbyopia technology including recently FDA-approved presbyopic IOLs like the Tecnis Symfony [Abbott Medical Optics, Abbott Park, Illinois] and corneal inlays, like the Raindrop [ReVision Optics, Lake Forest, California],” Dr. Chang said. However, he added, there are some people who don’t want surgery or who don’t want to do it yet for whatever reason, for whom the eye drop would be a compelling way of dealing with their presbyopia.

“I think it’s an elegant study that showed some nice preliminary results,” he said. One of the strengths here, in his view, is the fact that patients were separated into an older group of those age 50 and over and a younger group including those under age 50. “Our accommodation continues to deteriorate as we age,” Dr. Chang said. “So I think for the younger patients there was a slightly less effect of change, but that’s because they were better to begin with.” The effectiveness of the brimonidine/carbachol combination was in keeping with Dr. Chang’s expectations. “Having heard of this kind of result with brimonidine, pilocarpine, and other combination therapies, I think it’s interesting,” he said, adding that when the time comes, he could see himself trying such medications off-label as a drop winds its way through the FDA.

He does, however, have some minor concerns with the approach. “They did mention that there was a dull headache reported in 10% (of patients), and there was some difficulty in the luminosity that improved after a few weeks,” Dr. Chang said. “There was one patient who noticed it initially, but it did get better.” While not mentioned in the paper, Dr. Chang is also concerned that the miotic effect may be noticeable especially for light-eyed patients. “If you put a drop in that shrinks the pupil, are people going to look at you funny?” he said. Use of the drop, however, is reversible. That means that if patients don’t like it or the drop hurts, they can move on to the next option, he pointed out. “I think it’s a good intermediate step with a low barrier to entry,” Dr. Chang said. “Patients get a prescription, fill the drop, put it in, and if it works, great. If it doesn’t, then they could think about inlays or lens exchange with presbyopic IOLs.” Sherman Reeves, MD, partner, Minnesota Eye Consultants, Bloomington, Minnesota, likewise views the study as an interesting one that adds significantly to the literature on the topic. “They did it as double-masked and randomized placebo-controlled, so it’s a very well-written study and well conducted,” he said. “That gives a lot of credibility to the results.” While the younger population had a little bit better results, this was not surprising, he said, adding that both groups had significant improvement in their near vision.

In the past, similar drops have unfortunately not passed muster, Dr. Reeves pointed out. “Part of the problem with some of the miotics in the past has been too much pupillary miosis,” he said. “People were getting redness from the drop or brow ache.” However, the combination of carbachol and brimonidine allows some of the effects of brow aches and redness to be mitigated, he said, adding that the dosing could also be decreased a bit. Dr. Reeves thinks this could be an exciting potential option for presbyopia. “I think that this could potentially be very popular for patients because it’s a liquid eye drop approach,” Dr. Reeves said. “Use the drop in the morning and it lasts pretty much the working day and gives patients that extra near vision.” Also, given that this is a nonsurgical approach, he thinks that a lot of patients would be interested if such a drop became available. Dr. Reeves’ concern is that with miotics such as pilocarpine there’s sometimes a small risk of retinal detachment. “I think that risk is quite low,” he said, adding that high myopes might want to be a little more cautious for that reason. Overall, Dr. Reeves is optimistic about the approach. “I think this is an exciting avenue of development in the quest for presbyopia therapy,” he said, noting that there’s the potential for a large market for this miotic approach. “It could be a nice option for a lot of patients at that initial (presbyopic) step.”


1. Abdelkader A. Improved presbyopic vision with miotics. Eye Contact Lens. 2015;41:323–7.

Editors’ note: Drs. Chang and Reeves have no financial interests related to their comments.

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Reviewing miotic approach to presbyopia Reviewing miotic approach to presbyopia
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