Cyclosporine 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%

Restasis is the original cyclosporine formulation. It is a preservative-free anionic oil-in-water emulsion, where the cyclosporine is dissolved in castor oil.

• How it works: It uses polysorbate 80 as an emulsifying agent to keep the oil and water mixed.

• Patient Insight: Because it is an emulsion (rather than a clear solution), some patients report temporary blurred vision immediately after use.

Ikervis 0.1%

Ikervis is a cationic nanoemulsion, utilizing the same platform as Cationorm.

• How it works: It contains cetalkonium chloride, which gives the oil nanodroplets a net positive charge. Since the ocular surface is negatively charged, these droplets "stick" to the eye longer.

• The Advantage: It is hypothesized that the tear film’s lipid layer acts as a reservoir, slowly releasing cyclosporine over time. This high bioavailability allows for once-daily dosing, typically at bedtime.

Cequa 0.09%

Cequa utilizes nano-micelle technology. Cyclosporine is encased in a surfactant called Octoxynol 40 to form a "micelle"—a tiny sphere with a water-soluble exterior.

• How it works: These micelles are significantly smaller than the droplets in Restasis. This smaller size creates a massive increase in surface area, allowing the drug to bypass the tear film and penetrate the ocular tissue more efficiently.

• Clinical Impact: Research (Kuwano et al., 2002) suggests this formulation results in higher bioavailability and faster onset of action compared to traditional emulsions.

Vevye 0.1%

Vevye is a groundbreaking water-free cyclosporine drop that uses perfluorobutylpentane (SFA) as its delivery vehicle—a technology similar to NovaTears or Miebo.

• How it works: Because SFAs have very low surface tension, the drop spreads instantly and evenly across the eye without the need for surfactants or preservatives.

• The Result: Animal studies show Vevye delivers up to 22 times the amount of cyclosporine to the cornea compared to Restasis. For patients, the lack of water means a significantly lower risk of the "burning" sensation common with other brands.

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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