Preservatives are commonly used to prolong the shelf life of topical ophthalmic medications, but we have long been aware of the tradeoffs in ocular surface health, particularly for patients with glaucoma who often use chronic medication for years. In my practice, I have explored the current nonpreserved options for my patients, including nonpreserved combination drops that take some additional steps toward improving patients’ lives.

Nonpreserved Glaucoma Medications

The primary problem associated with preservatives is ocular-surface toxicity. For patients taking one or more intraocular pressure (IOP)-reducing medications once or twice a day for years, toxicity can have significant effects on quality of life. These patients can sometimes need additional therapy for ocular-surface disease, particularly if there is corneal or conjunctival staining. As an added problem, no one with irritated eyes wants to add more drops that cause additional discomfort on instillation, and this can negatively affect compliance. Adherence to drop therapy is already a well-known, significant barrier in effective IOP management. Toxicity and ocular surface damage also can affect the success of surgery in the future, whether it’s a cataract procedure or glaucoma surgery. With all of these disadvantages in mind, it’s easy to see the benefit to patients of a reduced preservative load on their cornea.

One very common preservative is benzalkonium chloride (BAK). Present in approximately 70% of glaucoma medications, BAK can elicit an allergic reaction, as well as ocular surface toxicity from long-term use.¹ Causing not only unstable tear film and the resulting dry-eye disease, BAK toxicity also can cause corneal and conjunctival damage.¹ Nonpreserved medications have been shown to offer the same efficacy as those with BAK in many cases, without the damaging side effects.²

Some of our more commonly used nonpreserved or alternatively preserved medications include a combination of the carbonic anhydrase inhibitor and beta blocker dorzolamide and timolol (Cosopt PF; Akorn), a formulation of the prostaglandin analog latanoprost (Xelpros; Sun Ophthalmics), and the 2 prostaglandin analogs, tafluprost (Zioptan; Merck) and travoprost (Travatan-Z; Novartis). There are preservative-free generic formulations for some medications as well, including brimonidine, dorzolamide, latanoprost, and timolol. Compounded glaucoma drugs (Simple Drops; ImprimisRx) give us access to individual medications like latanoprost and dorzolamide, as well as combinations with the trade names Tim-Lat, Brim-Dor, Tim-Dor-Lat, Tim-Brim-Dor, Tim-Brim-Dor-Lat, and Tim-Dor, the branded form of which has been subject to shortages.

Combining Preservative-free Drops

Ocular surface toxicity is a cause of noncompliance with glaucoma medications, but it is certainly not the only one. Busy people can easily forget to use their drops. Older patients in particular can have cognitive problems that prevent them from remembering their medications, and they can lack the vision and dexterity needed to use an eye-drop bottle accurately. Adding to these challenges, patients often need more than 1 medication to reach their target IOP, and those medications may be taken on different schedules. With each medication, compliance becomes worse.³

As a result, when patients need multiple medications, I’m inclined to choose a combination drop. Patients can enjoy the convenience of a single drop, while getting the benefits of 2 or more drugs. In my practice I have had success with nonpreserved Tim-Dor, as well as other combinations, such as Tim-Lat or Brim-Dor. For complex cases where I’m looking for additional potency and the complementary effects of different classes of drugs, I like to prescribe combinations of 3 or 4 drugs.

The commonly prescribed combination of timolol and latanoprost, and triple and quadruple combinations, are only available from a compounding pharmacy, which offers the flexibility of customizing combinations to fit specific needs. One example is a preservative-free combination not containing a beta-blocker. To ensure that the medications are of reliably high safety and quality, I look for strong accreditations in terms of quality standards, including 503A and 503B standards, accreditation from the Pharmacy Compounding Accreditation Board, and a pharmacy that can ship to all 50 states. In my experience, compounded combination drops can cost the same or less than buying generic drops individually in many situations, which is good news because cost can be a barrier to compliance as well.

Additional Compliance Support

Combination drops certainly offer the convenience that patients want. Patients would much rather take 1 drop than keep track of multiple drops and schedules. When patients use 2 name-brand drops from different manufacturers, however, they can experience another kind of inconvenience. There is a trend in branded pharmaceuticals where companies partner with specialty pharmacies that provide copay cards for their drugs. This helps ensure that patients have access to a particular product, but to get 2 medications, patients might need to go to 2 different specialty pharmacies.

When this process inconveniences the patient or my practice, I look to a combination drop as an alternative. In many cases, patients must travel to a pharmacy to pick up their medications. If we choose a compounded option, we submit the order electronically, and the preservative-free fixed-combination is mailed directly to the patient. It’s a significantly reduced burden for them, as well as an opportunity for our office to reduce pharmacy call-backs. And, of course, if patients have their medications on schedule, there are no gaps where IOP elevation could become a risk.

This popular convenience has become a lifeline in the COVID-19 environment, when patients don’t want to go to the pharmacy or are unable to even leave their senior living facility. I will continue to prescribe compounded medications as the uncertainty continues in the coming months. And I look forward to seeing more nonpreserved medications in the future, as well as more compounded options as proprietary rights change and we gain more options for additional classes of medications. GP

Jason Bacharach, MD, is the medical director and founding partner of North Bay Eye Associates, located in Sonoma County, California. He is also the chief of glaucoma services at California Pacific Medical Center in San Francisco. He reports consultancy to ImprimisRx and consultancy to and speaker’s fees from Sun Pharma. Reach him at jbacharach@northbayeye.com.

References

1. Aristeidis C, Dorotheos-Dimitrios T. Dry eye, contact lenses and preservatives in glaucoma medication. Clin Ophthalmol J. 2019;1(1):COJ-01-1003.
2. Aptel F, Pfeiffer N, Schmickler S, et al. Noninferiority of preservative-free versus bak-preserved latanoprost-timolol fixed combination eye drops in patients with open-angle glaucoma or ocular hypertension. J Glaucoma. 2019;28(6):498-506.
3. Patel SC, Spaeth GL. Compliance in patients prescribed eyedrops for glaucoma. Ophthalmic Surg. 1995;26(3):233-236.