Frequent red eyes is a warning that something is wrong with the surface of your eyes.

Using a redness relief eye drop to remove the redness may make you feel better temporarily but will eventually make you worse.

A vasoconstrictor eye drop is a “red eye relief” or “get the red out” over-the-counter eye drop.

The active ingredient in the eye drop stimulates receptors on the walls of blood vessels on the surface of the eye, causing the blood vessels to temporarily shrink. This reduces visible eye redness. These eye drops work because the skin of the eye (called the conjunctiva) is very thin, so the drug can penetrate it to reach the blood vessels.

There are two distinct types of receptors on the blood vessel walls that you should care about.

Alpha-1 receptors are located on arteries and veins. Activating alpha-1 receptors causes these blood vessels to shrink. Because arteries are constricted, blood flow to the surface of the eye is temporarily reduced, which decreases the supply of oxygen and nutrients.

Alpha-2b receptors are located primarily on veins. Activating alpha-2b receptors causes veins to shrink, which also decreases the amount of blood flowing in arteries – less blood out, less blood in. In theory, more blood – and therefore more oxygen and nutrients – reaches the surface of the eye when alpha-2b receptors are activated than when alpha-1 receptors are activated.

There are four active ingredients in the currently available OTC products:

Naphazoline, which activates alpha-1 and alpha-2b receptors

Tetrahydrozoline, which activates alpha-1 receptors

Phenylephrine, which activates alpha-1 receptors

Brimonidine tartrate, which activates alpha-2b receptors

Yes, for naphazoline, which is available in 0.012% and 0.03% products. The concentration will be clearly indicated on the box’s Drug Facts panel.

No for tetrahydrozoline, which is only available in 0.05% concentration.

No for phenylephrine, which is only available in 0.02% concentration.

No for brimonidine, which is only available OTC in 0.025% concentration.

All redness reliever eye drops contain some type of liquid, typically lubricants, saline, water, or a combination.

Preservatives are also required. Common preservatives include benzalkonium chloride, alcohol, chlorobutanol, and polyquaternium 42. Some products contain multiple preservatives. Because preservatives are considered inactive ingredients, a concentration (strength) is rarely specified.

Most eye drops contain several other inactive ingredients which are designed to adjust and stabilize the pH. Note this does not mean that the pH of a specific eye drop is close to neutral pH (which is 7.4).

Learn more about inactive eye drop ingredients here.

If your eyes are redder after the redness reliever eye drop wears off than before you used it, this is rebound.

If your usual redness reliever is working for shorter and shorter periods of time, this is tolerance (officially termed tachyphylaxis).

Rebound and tolerance typically happen together because they have the same underlying cause (explained below).

If you find that you are using a redness reliever eye drop more often than once per day, on many or most days, you are probably noticing rebound and you are definitely developing tolerance. Even once daily use can lead to tolerance and rebound.

Normally, alpha receptors are stimulated by norepinephrine, a molecule the body produces itself which keeps the blood vessels at the correct size to provide oxygen and nutrients. When alpha receptors are repeatedly stimulated by redness relief drops, the alpha receptors down-regulate. The number of receptors on blood vessel walls decreases, and each receptor becomes less responsive to stimulation by norepinephrine or one of the active ingredients listed above.

When the eye drop wears off, natural norepinephrine should take over and maintain a normal blood vessel size. However, when the alpha receptors are down-regulated, norepinephrine no longer signals blood vessels effectively. The blood vessels enlarge to a greater diameter than before the eye drop was used. This is rebound.

Eventually, the redness reliever eye drop stops working, or works for only a brief period of time, because there are too few alpha receptors to respond to the stimulation of the active ingredient. This is tolerance.

Some scientists believe that alpha-1 receptors are more likely to down-regulate than alpha-2 receptors.

Yes. Remember that most of these eye drops contain one or more preservatives.

Preservatives are irritating to the surface of the eye and can cause eye redness after only a few days of frequent use. Some patients may respond to preservative irritation by increasing their use of redness relief eye drops, which creates a vicious cycle of worsening redness, rebound and tolerance.

Preservatives can also cause or exacerbate dry eyes. Long-term, excessive use of preserved OTC eye drops can cause permanent dry eye disease.

Some patients are allergic to certain preservatives or other ingredients in OTC eye drops.

The pharmaceutical industry has responded to concerns about harm from eye drop preservatives by making preservative-free artificial tears. There is not yet a preservative-free OTC redness relief eye drop on the market.

Ideally these products should be “special occasion” eye drops only. Weddings are a good example.

If your eyes are red every day, and you use (or feel the need to use) a redness reliever eye drop every day, then there are underlying eye conditions and / or lifestyle issues causing the eye redness that need to be addressed.

Using a redness relief eye drop to manage dry eye disease, contact lens overwear, excessive screen time, or frequent cannabis use is ultimately going to make you worse.

For tips on managing red eyes due to cannabis use, the video series Managing High Eyes on this web site.

Lumify is a newer redness relief eye drop that primarily activates alpha-2b receptors on veins. Because Lumify primarily shrinks veins and not arteries, in theory this is healthier for the surface of the eye. If the eye surface is not starved of oxygen, when the Lumify wears off there may be less rebound enlargement of the blood vessels.

The clinical trials of Lumify did not show rebound between doses (it was used four times a day), or after the eye drop was stopped. However, these trials were for 4 to 5 weeks only. There is no data on what will happen if you use Lumify several times a day, every day, for longer periods of time.

Lumify is preserved with BAK. Using a BAK-preserved eye drop 2 to 4 times per day for months is likely to lead to BAK toxicity. If you have underlying dry eyes, frequent exposure to BAK may lead to permanent worsening of your dry eye disease.