Topical Ophthalmic Medication: Do Your Patients Get it?
By Marguerite B. McDonald, MD, FACS
Last month, we raised the issue of patients struggling to properly administer artificial tears or prescription eye drops, and the treatment repercussions of that difficulty.
But when topical ophthalmic medication fails to reach its target, we can’t simply blame patients’ poor aim or non-compliance. The fact is, the eye presents significant structural obstacles that can keep medication from reaching its target tissue.
The average size of a topical drop is 50 microliters. When you consider that the target for that drop – the ocular surface – is a reservoir of about 30 microliters, the problem becomes clear.
Given this mismatch, it should come as no surprise that spillage and nasolacrimal drainage is common. That spillage and draining often is exacerbated by tearing and blinking, which can dilute the medication that does reach the ocular surface. Tear film volume, which is about 7 microliters to 10 microliters, turns over at a rate of 0.5 to 2.2 microliters per minute.
The cornea is the primary route for topical drugs to be absorbed but offers significant anatomical and physiological barriers. What’s more, the conjunctiva and underlying sclera have a greater surface area than the cornea and are conduits to systemic absorption. And, there is less than five minutes of ocular surface contact time for any drop. All these factors combine to prevent all but about 5 percent of the original dose from reaching its target.
Fortunately, there now are several strategies available to facilitate greater corneal absorption and minimize precorneal medication loss.
Three of the more successful of these strategies, which were developed by drug designers, are:
Increasing the amount of medication able to provide benefit by increasing the dose and/or the frequency of administration;
Enhancing the medication’s molecular design by increasing lipophilicity and/or solubility; and
Altering formulation science by increasing viscosity, corneal penetration and residence time.
Of course, the effectiveness of any of these strategies ultimately depends on patient compliance. And each of these strategies may encourage some degree of non-compliance, albeit in different ways. For instance, low drug bioavailability usually requires a higher frequency of administration, a common reason for poor compliance.
Some molecular characteristics, such as lipophilicity, affect the formulation and, as a result, it may be necessary to shake the medication before administering, which may result in variability of the drug administered. This is particularly true of suspensions, which are dependent on resuspension, ie, shaking. When a patient does not shake the bottle as instructed, most of the drug sinks to the bottom and is delivered to the eye at the end of the course of treatment, when it is often less needed.
Poor compliance with shaking of prescription eye drop bottles is legendary. In a classic study by Apt and colleagues, published in 1979 in American Journal of Ophthalmology, 100 adult patients were given a bottle of an ophthalmic suspension medication labeled with the instructions: "Instill one drop in each eye four times daily. Shake well."1
"Shake well" was labeled in red to emphasize the point. The number of times the bottle was shaken by each patient was observed and recorded. Of the 100 patients in the study, 63 did not shake the bottle even once.
Sometimes, certain formulation characteristics, such as pH and excipients, are needed for drug delivery; these can result in low tolerability due to discomfort, blurred vision, etc.
Adding to these challenges, studies have documented variability in drop-to-drop volume from some bottles. Nascimento and colleagues published a study in which they concluded that this lack of uniformity produced drops that were inadequate to successfully treat the condition. This was especially true when drops were used for long treatment periods, such as the expensive drops indicated for glaucoma therapy.2
The challenges presented by topical ophthalmic drug therapy are daunting. However, there is one last strategy, not developed by drug makers, but which I have found extremely effective: having a technician stay behind in the exam lane for a minute or two to demonstrate the proper technique and to emphasize the importance of compliance. Even a few quick tips, such as refrigerating drops that sting, or shaking suspensions 20 times before administering each dose, are immensely helpful.
When it comes to compliance and effectively administering topical ophthalmologic drops, those few minutes of additional effort can spell the difference between a successful treatment regimen and one that fails.
Apt L, et al. Am J Ophthalmol. 1979;doi:10.1016/0002-9394(79)90145-4.
Nascimento VS, et al. Rev Bras Oftalmol. 2017;doi:10.5935/0034-7280.20170005.
Marguerite McDonald, MD, FACS, with OCLI on Long Island, NY, is clinical professor of Ophthalmology at NYU Langone Medical Center, NY, and clinical professor of Ophthalmology at Tulane University Health Sciences Center, New Orleans, Louisiana.