Cyclosprine Drops for Dry Eyes: A Comparison of Restasis, Cequa, Ikervis and Vevye
Welcome back.
Today, we'll be looking at an entire class of dry eye drops, the cyclosporine drops.
There are many commercially available products around the world. Restasis, Cequa, and Ikervis are some examples of cyclosporine eye drops available in Australia. Vevye is a new type of cyclosporine drop released in the United States.
What is Cyclosporine? How does Cyclosporine work?
Our Immune System
Whenever our immune system spots foreign objects, usually things like invading microbes, it recruits T cells to take them out. T cells are like the soldiers of the body, and they release a messenger chemical called cytokines to recruit more T cells. T cells and other inflammatory mediators cause the blood vessels nearby to expand. This rush of blood and fluid is what creates the familiar symptoms of inflammation, such as redness and heat, swelling and pain. Normally, inflammation is good—it helps the body fight off a potentially harmful invader. But in organ transplant or in chronic diseases like dry eyes, the T cells and cytokines never turn off. This results in chronic inflammation that keeps damaging the eye's surface and dries out your tear glands even more. The chronic inflammation makes the dry eye worse.
How Cyclosporin Stops the Cycle
Cyclosporine has been used for a long time as an immunosuppressant medication in preventing rejection after organ transplantation. Essentially, cyclosporine disrupts the T cells' ability to produce inflammatory cytokines. This stops the body from recruiting more T cells, thus breaking the cycle of inflammation. This gives the surface of your eye a chance to heal, allows your tear glands to recover, and ultimately helps your eye produce better, more stable tears.
The delivery mechanism is a key differentiating factor in commercially available eye drops, as cyclosporine itself doesn't dissolve in the tear film very well and cannot penetrate the cornea very easily.
Restasis (0.05%) vs Cequa (0.09%) vs Ikervis (0.1%) vs Vevye (0.1%):
Restasis is one of the earliest cyclosporine eye drops commercially available. It is a preservative-free anionic oil-in-water emulsion, contains cyclosporine dissolved in castor oil with polysorbate 80 as the emulsifying agent. Ikervis is a cationic nanoemulsion, like Cationorm. In fact, they are made by the same company. Ikervis contains cetalkonium chloride, which acts as an emulsifier as well as a cationic surfactant. It is found that due to the net positive charge of the oil nanodroplets, the cyclosporine stays on the eye for longer. Furthermore, it is hypothesised that the tear film lipid layer would act as a reservoir for unused cyclosporine nanodroplets to be released later. The combination of these effects, as well as higher dosage strength, could very likely explain the difference in dosing regimen between once-a-day Ikervis versus twice-a-day Restasis.
Cequa uses a nano-micelle technology, where cyclosporine is dissolved in castor oil, which is then trapped in a surfactant called Octoxynol 40 to form a micelle. Cequa contains a much smaller micelle size compared to the nanoparticles found in Ikervis and Restasis. A smaller micelle size effectively increases the total surface area the drug can interact with the eye, resulting in higher bioavailability, faster interactions and faster penetration into the eye.
A study by Kuwano et al (2002) found that the concentration of cyclosporine delivered with the micelle-based formulation (i.e. Cequa) resulted in much higher cyclosporine concentration in the cornea, compared to the emulsion-based formulation and the oil-based formulation.
A more recently released cyclosporine eye drop called Vevye utilises perfluorobutylpentane as a delivery vehicle. This is likely something similar to perfluorohexyloctane used in previously discussed eyedrops Novatears/Evotears/Miebo. Animal studies have found a significantly increased amount of cyclosporine in the cornea, even hours after the initial drop, suggesting that Vevye is going to be even more effective for dry eye treatment than the other cyclosporine drops.
How to reduce the stinging sensation from cyclosporine eye drops?
One of the main side effects of using cyclosporine eye drops is that they sting. A lot. The main method we use in clinical practice to reduce the stinging is to prepare the eye with corticosteroids and lubricating drops, for example, FML and Systane Hydration, for a month before starting the cyclosporine eye drops.
Verdict:
Before writing this article, I would have preferred Ikervis over the other drops purely because of the fact that you only need to use it once a day, which is a significant improvement in terms of quality of life. However, after writing this article, I think Vevye should be strongly considered before the other drops, but it is not available in Australia, so I have no personal experience with it. Online feedback from Reddit appears to be very positive. Nevertheless, efficacy is often individual, and your doctor will work with you to find the most effective treatment.
References
Lallemand, F., Schmitt, M., Bourges, J.-L., Gurny, R., Benita, S., & Garrigue, J.-S. (2017). Cyclosporine A delivery to the eye: A comprehensive review of academic and industrial efforts. European Journal of Pharmaceutics and Biopharmaceutics, 117, 14–28. https://doi.org/10.1016/j.ejpb.2017.03.006
Kuwano, M., Ibuki, H., Morikawa, N., Ota, A., & Kawashima, Y. (2002). Cyclosporine A formulation affects its ocular distribution in rabbits. Pharmaceutical Research, 19, 108–111.
Novartis. (n.d.). Drug product components. Vevye. Retrieved from https://vevye.com/hcp/vehicle
Sun Pharma. (n.d.). How Cequa works. Retrieved from https://www.cequa.com/how-cequa-works
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