New nonpreserved drop for dry eye combines the active ingredient cyclosporine A with dextran, glycerol, and hydroxypropylmethylcellulose in a chondroitin sulfate emulsion.
In the treatment of chronic dry eye, cost and compliance with topical medications have been ongoing problems. We know that medications like Restasis (Allergan) and Xiidra (Shire) work well, but for a patient with a high-deductible insurance plan, they may cost $400-$500 per month out of pocket.
A new therapeutic eye drop has become available that has the potential to help patients with both cost and compliance issues. Klarity-C (Imprimis Pharmaceuticals) is a compounded, nonpreserved eye drop for the treatment of dry eye. It combines the active ingredient cyclosporine A 0.1% with several lubricants (dextran, glycerol, and hydroxypropylmethylcellulose) in a chondroitin sulfate emulsion.
The company also offers the Klarity chondroitin sulfate diluent alone (without any active ingredient). As a compounding pharmacy, the company could add a corticosteroid or some other agent to custom formulations of the drop if such formulations are requested by physicians. Cyclosporine A is known for its ability to inhibit T-cell activation and cytokine release, reducing the T-cell-mediated inflammation that has been implicated in ocular surface disease.
Michelle K. Rhee, MD, and Francis S. Mah, MD, recently published a comprehensive review of the clinical utility of cyclosporine 0.05%, noting that it has been shown to stimulate natural tear production, and increase goblet cell density.1 A number of studies have shown an impact on dry eye signs, such as corneal staining, with some reduction in symptoms, as well.1 Klarity-C drops contain twice the concentration of cyclosporine that is in Restasis (0.1% versus 0.05%), so we can expect the drops to be at least as effective and perhaps more effective due to the higher concentration.
Dilly of a diluent
I’m enthusiastic about the potential for the chondroitin sulfate vehicle or diluent in these drops. This molecule has been widely used in corneal storage media (Optisol GS) and in several ophthalmic viscoelastic devices. In research I participated in years ago at the University of Minnesota, we found chondroitin sulfate to be more protective of the corneal endothelial and epithelial cells than sodium hyaluronate, which is in the same family of glycosaminoglycans.
It has mild anti-inflammatory properties2, as well as cell membrane-stabilizing properties that reduce cell death and promote healing. From extensive experience with chondroitin sulfate as a storage medium for corneal tissue, we also know that it reduces corneal edema, which could be beneficial to corneas that are under stress from ocular surface disease.
Finally, chondroitin sulfate is an excellent topical lubricant3 (Figure 1) with minimal to no spectacle blur or irritation on instillation. That is important because burning or stinging on instillation and transient blur often discouraged patients from using their cyclosporine drops in the past, especially during the first 8 to 12 weeks before the drug had a chance to take effect.
Use in practice
The recommended initial dosing will be twice daily, the same as for other topical T-cell mediators. In the past, I have found it possible for patients to drop down to a once-daily maintenance dose of cyclosporine after a year or so of b.i.d. treatment. My intent is to take the same approach with the Klarity-C. However, because it is unpreserved, we also have the flexibility to recommend that patientswith severe dry eye or high-risk corneal transplants use it more frequently than twice a day.
Klarity-C is currently available as a 503(a) compounded drug, which means that it must be ordered for each specific patient. However, it is manufactured in a 503(b) certified facility and should eventually be available under the 503(b) program, which allows clinicians to order a supply prior to writing individual prescriptions.
It is important to make sure, whenever possible, that the compounded or generic medications we use are produced in 503(b)-certified facilities. These are facilities that have met the same highquality standards for manufacturing as branded pharmaceutical manufacturers.
This is an exciting time for dry eye. There are a number of new innovations in the pipeline, both for new formulations and delivery mechanisms for existing drugs like cyclosporine and for agents with new mechanisms of action. As we evaluate new treatments, it is wise to consider cost and patient compliance factors in our decision-making.
Richard L. Lindstrom, MD
P: 612/813-3633 E: [email protected]
Dr. Lindstrom is adjunct professor emeritus, Department of Ophthalmology, University of Minnesota, and founder and managing partner of Minnesota Eye Consultants in Minneapolis. He holds a patent on Klarity-C and is a consultant/investor in Imprimis. He consults for many other dry eye companies, including Kala, Novabay, Ocular Therapeutix, Omega Eye Health, Sun Pharma, and TearLab.
1. Rhee MK, Mah FS. Clinical utility of cyclosporine ophthalmic emulsion 0.05% for symptomatic relief in people with chronic dry eye: A review of the literature. Clin Ophthalmol 2017;11:1157-66.
2. Moon JW, Lee H-J, Shin KC, et al. Short term effectsof topical cyclosporine and viscoelastic on the ocular surfaces in patients with dry eye. Korean J Ophthalmol 2007;21(4):189-94.
3. Llamas-Moreno JF, Baiza-Durán LM, SaucedoRodríguez LR, Alaníz-De la O JF. Efficacy and safety of chondroitin sulfate/xanthan gum versus polyethylene glycol/propylene glycol/hydroxypropyl guar in patients with dry eye. Clin Ophthalmol 2013;7:995-9.